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Nitric Oxide: A True Inflammatory Mediator

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Nitric Oxide

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 143))

Abstract

Nitric oxide (NO) is a colorless gas at room temperature and is one of the simplest molecules known. For more than 300 years, it was considered mainly as an environmental pollutant and product of bacterial metabolism. Important discoveries in the 1980s showed that NO can be synthesized by mammalian cells, and it has since been implicated in a wide variety of regulatory mechanisms ranging from vasodilatation and blood-pressure control to neurotransmission (MONCADA and HIGGS 1993). NO is also involved in non-specific immunity and participates in the complex mechanism of tissue injury, acting as a major mediator of inflammatory processes and apoptosis. This work reviews the data showing that NO plays an important and complex role in inflammatory and autoimmune diseases.

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References

  • Abbas AK, Murphy KM, Sher A (1996) Functional diversity of helper T lymphocytes. Nature 383:787–793

    PubMed  CAS  Google Scholar 

  • Adamson DC, Wildemann B, Sasaki M, Glass JD, McArthur JC, Christov VI, Dawson TM, Dawson VL (1996) Immunologic NO synthase: elevation in severe AIDS dementia and induction by HIV-1 gp41. Science 274:1917–1921

    PubMed  CAS  Google Scholar 

  • Amin A, Di Cesare PE, Vyas P, Attur M, Tzeng E, Billiar TR, Stuchin SA, Abramson SB (1995) The expression and regulation of nitric oxide synthase in human osteoarthritis-affected chondrocytes: evidence for up-regulated neuronal nitric oxide synthase. J Exp Med 182:2097–2102

    PubMed  CAS  Google Scholar 

  • Bagasra O, Michaels FH, Zheng YM, Bobroski LE, Spitsin SV, Fu ZF, Tawadros R, Koprowski H (1995) Activation of the inducible form of nitric oxide synthase in the brains of patients with multiple sclerosis. Proc Natl Acad Sci USA 92:12041–12045

    PubMed  CAS  Google Scholar 

  • Barnes PJ (1996) Pathophysiology of asthma. Br J Clin Pharmacol 42:3–10

    PubMed  CAS  Google Scholar 

  • Barton BE, Jackson JV (1993) Protective role of interleukin 6 in the lipopolysaccharide-galactosamine septic shock model. Infect Immun 61:1496–1499

    PubMed  CAS  Google Scholar 

  • Bastian NR, Xu S, Shao XL, Shelby J, Granger DL, Hibbs JBJ (1994) N ω-monomethyl-L-arginine inhibits nitric oxide production in murine cardiac allografts but does not affect graft rejection. Biochim Biophys Acta 1226:225–231

    PubMed  CAS  Google Scholar 

  • Bauer H, Jung T, Tsikas D, Stichtenoth DO, Frolich JC, Neumann C (1997) Nitric oxide inhibits the secretion of T-helper 1-and T-helper 2-associated cytokines in activated human T cells. Immunology 90:205–211

    PubMed  CAS  Google Scholar 

  • Beckman JS, Koppenol WH (1996) Nitric oxide, Superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol 271:C1424–C1437

    PubMed  CAS  Google Scholar 

  • Beckmann JS, Ye YZ, Anderson PG, Chen J, Accavitti MA, Tarpey MM, White CR (1994) Extensive nitration of protein tyrosines in human atherosclerosis detected by immunohistochemistry. Biol Chem Hoppe Seyler 375:81–88

    PubMed  CAS  Google Scholar 

  • Belmont HM, Levartovsky D, Goel A, Amin A, Giorno R, Rediske J, Skovron ML, Abramson SB (1997) Increased nitric oxide production accompanied by the upregulation of inducible nitric oxide synthase in vascular endothelium from patients with systemic lupus erythematosus. Arthritis Rheum 40:1810–1816

    PubMed  CAS  Google Scholar 

  • Billiar TR (1995) Nitric oxide. Novel biology with clinical relevance. Ann Surg 221:339–349

    PubMed  CAS  Google Scholar 

  • Billiar TR, Curran RD, Harbrecht BG, Stuehr DJ, Demetris AJ, Simmons RL (1990) Modulation of nitrogen oxide synthesis in vivo: N G-monomethyl-L-arginine inhibits endotoxin-induced nitrate/nitrate biosynthesis while promoting hepatic damage. J Leukoc Biol 48:565–569

    PubMed  CAS  Google Scholar 

  • Bingisser RM, Tilbrook PA, Holt PG, Kees UR (1998) Macrophage-derived nitric oxide regulates T cell activation via reversible disruption of the Jak3/STAT5 signaling pathway. J Immunol 160:5729–5734

    PubMed  CAS  Google Scholar 

  • Bogdan C, Vodovotz Y, Paik J, Xie QW, Nathan C (1994) Mechanism of suppression of nitric oxide synthase expression by interleukin-4 in primary mouse macrophages. J Leukoc Biol 55:227–233

    PubMed  CAS  Google Scholar 

  • Bogdan C, Thuring H, Dlaska M, Rollinghoff M, Weiss G (1997) Mechanism of suppression of macrophage nitric oxide release by IL-13: influence of the macrophage population. J Immunol 159:4506–4513

    PubMed  CAS  Google Scholar 

  • Bonta IL, Ben-Efraim S (1993) Involvement of inflammatory mediators in macrophage antitumor activity. J Leukoc Biol 54:613–626

    PubMed  CAS  Google Scholar 

  • Brenner T, Brocke S, Szafer F, Sobel RA, Parkinson JF, Perez DH, Steinman L (1997) Inhibition of nitric oxide synthase for treatment of experimental autoimmune encephalomyelitis. J Immunol 158:2940–2946

    PubMed  CAS  Google Scholar 

  • Brouet I, Ohshima H (1995) Curcumin, an anti-tumour promoter and antiinflammatory agent, inhibits induction of nitric oxide synthase in activated macrophages. Biochem.Biophys Res Commun 206:533–540

    PubMed  CAS  Google Scholar 

  • Bruch-Gerharz D, Fehsel K, Suschek C, Michel G, Ruzicka T, Kolb-Bachofen V (1996) A proinflammatory activity of interleukin 8 in human skin: expression of the inducible nitric oxide synthase in psoriatic lesions and cultured keratinocytes. J Exp Med 184:2007–2012

    PubMed  CAS  Google Scholar 

  • Bult H (1996) Nitric oxide and atherosclerosis: possible implications for therapy. Mol Med Today 2:510–518

    PubMed  CAS  Google Scholar 

  • Bulut V, Severn A, Liew FY (1993) Nitric oxide production by murine macrophages is inhibited by prolonged elevation of cyclic AMP. Biochem Biophys Res Commun 195:1134–1138

    PubMed  CAS  Google Scholar 

  • Buster BL, Weintrob AC, Townsend GC, Scheid WM (1995) Potential role of nitric oxide in the pathophysiology of experimental bacterial meningitis in rats. Infect Immun 63:3835–3839

    PubMed  CAS  Google Scholar 

  • Buttery LD, Springall DR, Chester AH, Evans TJ, Standfield EN, Parums DV, Yacoub MH, Polak JM (1996) Inducible nitric oxide synthase is present within human atherosclerotic lesions and promotes the formation and activity of peroxynitrite. Lab Invest 75:77–85

    PubMed  CAS  Google Scholar 

  • Cattell V, Cook HT, Ebrahim H, Waddington SN, Wei XQ, Assmann KJ, Liew FY (1998) Anti-GBM glomerulonephritis in mice lacking nitric oxide synthase type 2. Kidney Int 53:932–936

    PubMed  CAS  Google Scholar 

  • Chang RH, Feng MH, Liu WH, Lai MZ (1997) Nitric oxide increased interleukin-4 expression in T lymphocytes. Immunology 90:364–369

    PubMed  CAS  Google Scholar 

  • Clancy RM, Amin AR, Abramson SB (1998) The role of nitric oxide in inflammation and immunity. Arthritis Rheum 41:1141–1151

    PubMed  CAS  Google Scholar 

  • Cobb JP, Buchman TG, Chang K, Qiu Y, Laubach VE, Karl IE, Hotchkiss RS. iNOS gene deficiency increases the mortality of sepsis in mice. Sixtieth Annual Meeting of The Society of University Surgeons, 77:2-11-1999. New Orleans

    Google Scholar 

  • Corbett JA, Kwon G, Turk J, McDaniel ML (1993a) IL-1 beta induces the coexpression of both nitric oxide synthase and cyclooxygenase by islets of Langerhans: activation of cyclooxygenase by nitric oxide. Biochemistry 32:13767–13770

    PubMed  CAS  Google Scholar 

  • Corbett JA, Sweetland MA, Wang JL, Lancaster JRJ, McDaniel ML (1993b) Nitric oxide mediates cytokine-induced inhibition of insulin secretion by human islets of Langerhans. Proc Natl Acad Sci USA 90:1731–1735

    PubMed  CAS  Google Scholar 

  • Cross AH, Misko TP, Lin RF, Hickey WF, Trotter JL, Tilton RG (1994) Aminoguanidine, an inhibitor of inducible nitric oxide synthase, ameliorates experimental autoimmune encephalomyelitis in SJL mice. J Clin Invest 93:2684–2690

    PubMed  CAS  Google Scholar 

  • Cross AH, Manning PT, Stern MK, Misko TP (1997) Evidence for the production of peroxynitrite in inflammatory CNS demyelination. J Neuroimmunol 80:121–130

    PubMed  CAS  Google Scholar 

  • Cross AH, Manning PT, Keeling RM, Schmidt RE, Misko TP (1998) Peroxynitrite formation within the central nervous system in active multiple sclerosis. J Neuroimmunol 88:45–56

    PubMed  CAS  Google Scholar 

  • Cuzzocrea S, Zingarelli B, Hake P, Salzman AL, Szabo C (1998a) Antiinflammatory effects of mercaptoethylguanidine, a combined inhibitor of nitric oxide synthase and peroxynitrite scavenger, in carrageenan-induced models of inflammation. Free Radic Biol Med 24:450–459

    PubMed  CAS  Google Scholar 

  • Cuzzocrea S, Zingarelli B, Villari D, Caputi AP, Longo G (1998b) Evidence for in vivo peroxynitrite production in human chronic hepatitis. Life Sci 63:L25–L30

    Google Scholar 

  • Cuzzocrea S, Zingarelli B, Costantino G, Caputi AP (1999) Beneficial effects of Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP), a Superoxide dismutase mimetic, in carrageenan-induced pleurisy. Free Radic Biol Med 26:25–33

    PubMed  CAS  Google Scholar 

  • De Groot CJ, Ruuls SR, Theeuwes JW, Dijkstra CD, Van der Valk P (1997) Immunocytochemical characterization of the expression of inducible and constitutive isoforms of nitric oxide synthase in demyelinating multiple sclerosis lesions. J Neuropathol Exp Neurol 56:10–20

    PubMed  Google Scholar 

  • De Vera ME, Shapiro RA, Nüssler AK, Mudgett JS, Simmons RL, Morris SMJ, Billiar TR, Geller DA (1996) Transcriptional regulation of human inducible nitric oxide synthase (NOS2) gene by cytokines: initial analysis of the human NOS2 promoter. Proc Natl Acad Sci USA 93:1054–1059

    PubMed  Google Scholar 

  • Di Rosa M, Ialenti A, Ianaro A, Sautebin L (1996) Interaction between nitric oxide and cyclooxygenase pathways. Prostagl Leukotr Essential Fatty Acids 54:229–238

    Google Scholar 

  • Ding M, Zhang M, Wong JL, Rogers NE, Ignarro LJ, Voskuhl RR (1998) Antisense knockdown of inducible nitric oxide synthase inhibits induction of experimental autoimmune encephalomyelitis in SJL/J mice. J Immunol 160:2560–2564

    PubMed  CAS  Google Scholar 

  • Efron DT, Kirk SJ, Regan MC, Wasserkrug HL, Barbul A (1991) Nitric oxide generation from L-arginine is required for optimal human peripheral blood lymphocyte DNA synthesis. Surgery 110:327–334

    PubMed  CAS  Google Scholar 

  • Evans CH (1995) Nitric oxide: what role does it play in inflammation and tissue destruction? Agents Actions Suppl 47:107–116, 107-116

    PubMed  CAS  Google Scholar 

  • Falzarano G, Krenger W, Snyder KM, Delmonte JJ, Karandikar M, Ferrara JL (1996) Suppression of B-cell proliferation to lipopolysaccharide is mediated through induction of the nitric oxide pathway by tumor necrosis factor-alpha in mice with acute graft-versus-host disease Blood 87:2853–2860

    PubMed  CAS  Google Scholar 

  • Fang FC (1997) Perspectives series: host/pathogen interactions. Mechanisms of nitric oxide-related antimicrobial activity. J Clin Invest 99:2818–2825

    PubMed  CAS  Google Scholar 

  • Fenyk-Melody JE, Garrison AE, Brunnert SR, Weidner JR, Shen F, Shelton BA, Mudgett JS (1998) Experimental autoimmune encephalomyelitis is exacerbated in mice lacking the NOS2 gene. J Immunol 160:2940–2946

    PubMed  CAS  Google Scholar 

  • Fletcher DS, Widmer WR, Luell S, Christen A, Orevillo C, Shah S, Visco D (1998) Therapeutic administration of a selective inhibitor of nitric oxide synthase does not ameliorate the chronic inflammation and tissue damage associated with adjuvant-induced arthritis in rats. J Pharmacol Exp Ther 284:714–721

    PubMed  CAS  Google Scholar 

  • Ford H, Watkins S, Reblock K, Rowe M (1997) The role of inflammatory cytokines and nitric oxide in the pathogenesis of necrotizing enterocolitis. J Pediatr Surg 32:275–282

    PubMed  CAS  Google Scholar 

  • Fukatsu K, Saito H, Fukushima R, Inoue T, Lin MT, Inaba T, Muto T (1995) Detrimental effects of a nitric oxide synthase inhibitor (N ω-nitro-L-argininemethyl-ester) in a murine sepsis model. Arch Surg 130:410–414

    PubMed  CAS  Google Scholar 

  • Fukumoto Y, Shimokawa H, Kozai T, Kadokami T, Kuwata K, Yonemitsu Y, Kuga T, Egashira K, Sueishi K, Takeshita A (1997) Vasculoprotective role of inducible nitric oxide synthase at inflammatory coronary lesions induced by chronic treatment with interleukin-lbeta in pigs in vivo. Circulation 96:3104–3111

    PubMed  CAS  Google Scholar 

  • Gabbai FB, Boggiano C, Peter T, Khang S, Archer C, Gold DP, Kelly CJ (1997) Inhibition of inducible nitric oxide synthase intensifies injury and functional deterioration in autoimmune interstitial nephritis. J Immunol 159:6266–6275

    PubMed  CAS  Google Scholar 

  • Gilkeson GS, Mudgett JS, Seldin MF, Ruiz P, Alexander AA, Misukonis MA, Pisetsky DS, Weinberg JB (1997) Clinical and serologie manifestations of autoimmune disease in MRL-lpr/lpr mice lacking nitric oxide synthase type 2. J Exp Med 186:365–373

    PubMed  CAS  Google Scholar 

  • Glauser MP, Zanetti G, Baumgartner JD, Cohen J (1991) Septic shock: pathogenesis. Lancet 338:732–736

    PubMed  CAS  Google Scholar 

  • Godkin AJ, De Beider AJ, Villa L, Wong A, Beesley JE, Kane SP, Martin JF (1996) Expression of nitric oxide synthase in ulcerative colitis. Eur J Clin Invest 26:867–872

    PubMed  CAS  Google Scholar 

  • Gold DP, Schroder K, Powell HC, Kelly CJ (1997) Nitric oxide and the immunomodulation of experimental allergic encephalomyelitis. Eur J Immunol 27:2863–2869 Goto M, Yamaguchi Y, Ichiguchi O, Miyanari N, Akizuki E, Matsumura F, Matsuda T

    PubMed  CAS  Google Scholar 

  • Mori K, Ogawa M (1997) Phenotype and localization of macrophages expressing inducible nitric oxide synthase in rat hepatic allograft rejection. Transplantation 64:303–310

    PubMed  Google Scholar 

  • Grabowski PS, Wright PK, Van’t H, Helfrich MH, Ohshima H, Ralston SH (1997) Immunolocalization of inducible nitric oxide synthase in synovium and cartilage in rheumatoid arthritis and osteoarthritis. Br J Rheumatol 36:651–655

    PubMed  CAS  Google Scholar 

  • Green LC, Tannenbaum SR, Goldman P (1981) Nitrate synthesis in the germ-free and conventional rat Science 212:56–58

    Google Scholar 

  • Groeneveld PH, Kwappenberg KM, Langermans JA, Nibbering PH, Curtis L (1997) Relation between pro-and anti-inflammatory cytokines and the production of nitric oxide (NO) in severe sepsis. Cytokine 9:138–142

    PubMed  CAS  Google Scholar 

  • Gupta SK, Fitzgerald JF, Chong SK, Croffie JM, Garcia JG (1998) Expression of inducible nitric oxide synthase (iNOS) mRNA in inflamed esophageal and colonic mucosa in a pediatric population. Am J Gastroenterol 93:795–798

    PubMed  CAS  Google Scholar 

  • Guslandi M (1998) Nitric oxide and inflammatory bowel diseases. Eur J Clin Invest 28:904–907

    PubMed  CAS  Google Scholar 

  • Halliwell B (1997) What nitrates tyrosine? Is nitrotyrosine specific as a biomarker of peroxynitrite formation in vivo? FEBS Lett 411:157–160 Hamid Q, Springall DR, Riveros-Moreno V, Chanez P, Howarth P, Redington A

    PubMed  CAS  Google Scholar 

  • Bousquet J, Godard P, Holgate S, Polak JM (1993) Induction of nitric oxide synthase in asthma. Lancet 342:1510–1513

    PubMed  Google Scholar 

  • Handy RL, Moore PK (1998) A comparison of the effects of L-NAME, 7-NI and L-NIL on carrageenan-induced hindpaw oedema and NOS activity. Br J Pharmacol 123:1119–1126

    PubMed  CAS  Google Scholar 

  • Harbrecht BG, Billiar TR, Stadler J, Demetris AJ, Ochoa J, Curran RD, Simmons RL (1992) Inhibition of nitric oxide synthesis during endotoxemia promotes intrahepatic thrombosis and an oxygen radical-mediated hepatic injury. J Leukoc Biol 52:390–394

    PubMed  CAS  Google Scholar 

  • Harbrecht BG, Stadler J, Demetris AJ, Simmons RL, Billiar TR (1994) Nitric oxide and prostaglandins interact to prevent hepatic damage during murine endotoxemia. Am J Physiol 266:G1004–G1010

    PubMed  CAS  Google Scholar 

  • Harbrecht BG, Kim YM, Wirant EA, Simmons RL, Billiar TR (1997) Timing of prostaglandin exposure is critical for the inhibition of LPS-or IFN-γ-induced macrophage NO synthesis by PGE2. J Leukoc Biol 61:712–720

    PubMed  CAS  Google Scholar 

  • Heeringa P, van Goor H, Moshage H, Klok PA, Huitema MG, de Jager A, Schep AJ Kallenberg CG (1998) Expression of iNOS, eNOS, and peroxynitrite-modified proteins in experimental anti-myeloperoxidase associated crescentic glomerulonephritis. Kidney Int 53:382–393

    PubMed  CAS  Google Scholar 

  • Herulf M, Ljung T, Hellstrom PM, Weitzberg E, Lundberg JO (1998) Increased luminal nitric oxide in inflammatory bowel disease as shown with a novel minimally invasive method. Scand J Gastroenterol 33:164–169

    PubMed  CAS  Google Scholar 

  • Hibbs JB, Taintor RR, Vavrin Z (1987) Macrophage cytotoxicity: Role for L-arginine deiminase and imino nitrogen oxidation to nitrite. Science 235:473–476

    PubMed  CAS  Google Scholar 

  • Hibbs JBJr, Taintor RR, Vavrin Z, Rachlin EM (1988) Nitric Oxide: a cytotoxic activated macrophage effector molecule. Biochem Biophys Res Commun 157:87–94

    PubMed  CAS  Google Scholar 

  • Hickey MJ, Sharkey KA, Sihota EG, Reinhardt PH, MacMicking JD, Nathan C, Kubes P (1997) Inducible nitric oxide synthase-deficient mice have enhanced leukocyteendothelium interactions in endotoxemia. FASEB J 11:955–964

    PubMed  CAS  Google Scholar 

  • Hierholzer C, Harbrecht B, Menezes JM, Kane J, MacMicking J, Nathan CF, Peitzman AB, Billiar TR, Tweardy DJ (1998) Essential role of induced nitric oxide in the initiation of the inflammatory response after hemorrhagic shock. J Exp Med 187:917–928

    PubMed  CAS  Google Scholar 

  • Hirsch EC, Hunot S, Damier P, Faucheux B (1998) Glial cells and inflammation in Parkinson’s disease: a role in neurodegeneration? Ann Neurol 44:S115–S120

    PubMed  CAS  Google Scholar 

  • Hoey S, Grabowski PS, Ralston SH, Forrester JV, Liversidge J (1997) Nitric oxide accelerates the onset and increases the severity of experimental autoimmune uveoretinitis through an IFN-gamma-dependent mechanism. J Immunol 159:5132–5142

    PubMed  CAS  Google Scholar 

  • Hoffman RA, Langrehr JM, Berry LM, White DA, Schattenfroh NC, McCarthy SA, Simmons RL (1996) Bystander injury of host lymphoid tissue during murine graftverus-host disease is mediated by nitric oxide. Transplantation 61:610–618

    PubMed  CAS  Google Scholar 

  • Hoffman RA, Nüssler NC, Gleixner SL, Zhang G, Ford HR, Langrehr JM, Demetris AJ, Simmons RL (1997) Attenuation of lethal graft-versus-host disease by inhibition of nitric oxide synthase. Transplantation 63:94–100

    PubMed  CAS  Google Scholar 

  • Hooper DC, Bagasra O, Marini JC, Zborek A, Ohnishi ST, Kean R, Champion JM, Sarker AB, Bobroski L, Farber JL, Akaike T, Maeda H, Koprowski H (1997) Prevention of experimental allergic encephalomyelitis by targeting nitric oxide and peroxynitrite: implications for the treatment of multiple sclerosis. Proc Natl Acad Sci USA 94:2528–2533

    PubMed  CAS  Google Scholar 

  • Howard M, Muchamuel T, Andrade S, Menon S (1993) Interleukin 10 protects mice from lethal endotoxemia. J Exp Med 177:1205–1208

    PubMed  CAS  Google Scholar 

  • Hughes FJ, Buttery LK, Hukkanen MJ, O’Donnell A, Maclouf J, Polak JM (1999) Cytokine-induced prostaglandin E2 synthesis and cyclooxygenase-2 activity are regulated both by a nitric oxide-dependent and — independent mechanism in rat osteoblasts in vitro. J Biol Chem 274:1776–1782

    PubMed  CAS  Google Scholar 

  • Inoue T, Fukuo K, Morimoto S, Koh E, Ogihara T (1993) Nitric oxide mediates interleukin-1-induced prostaglandin E2 production by vascular smooth muscle cells. Biochem Biophys Res Commun 194:420–424

    PubMed  CAS  Google Scholar 

  • Iyengar R, Stuehr DJ, Marietta MA (1987) Macrophage synthesis of nitrite, nitrate, and N-nitrosamines: Precursors and role of the respiratory burst. Proc Natl Acad Sci USA 84:6369–6373

    PubMed  CAS  Google Scholar 

  • James SL (1995) Role of nitric oxide in parasitic infections. Microbiol Rev 59:533–547

    PubMed  CAS  Google Scholar 

  • Johnson AW, Land JM, Thompson EJ, Bolanos JP, Clark JB, Heales SJ (1995) Evidence for increased nitric oxide production in multiple sclerosis. J Neurol Neurosurg Psychiatry 58:107–200

    PubMed  CAS  Google Scholar 

  • Kamisaki Y, Wada K, Ataka M, Yamada Y, Nakamoto K, Ashida K, Kishimoto Y (1997) Lipopolysaccharide-induced increase in plasma nitrotyrosine concentrations in rats. Biochim Biophys Acta 1362:24–28

    PubMed  CAS  Google Scholar 

  • Kashem A, Endoh M, Yano N, Yamauchi F, Nomoto Y, Sakai H (1996) Expression of inducible-NOS in human glomerulonephritis: the possible source is infiltrating monocytes/macrophages. Kidney Int 50:392–399

    PubMed  CAS  Google Scholar 

  • Kausalya S, Nath J (1998) Interactive role of nitric oxide and Superoxide anion in neutrophil-mediated endothelial cell injury. J Leukoc Biol 64:185–191

    PubMed  CAS  Google Scholar 

  • Kepka-Lenhart D, Chen L-C, Morris SM (1996) Novel actions of aspirin and sodium salicylate: discordant effects on nitric oxide synthesis and induction of nitric oxide synthase mRNA in a murine macrophage cell line. J Leukoc Biol 59:840–846

    PubMed  CAS  Google Scholar 

  • Kilbourn RG, Gross SS, Jubran A, Adams J, Griffith OW, Levi R, Lodato RF (1990) N G-methyl-L-arginine inhibits tumor necrosis factor-induced hypotension: implications for the involvement of nitric oxide. Proc Natl Acad Sci USA 87:3629–3632

    PubMed  CAS  Google Scholar 

  • Kim YM, Talanian RV, Li J, Billiar TR (1998) Nitric oxide prevents IL-lbeta and IFN-gamma-inducing factor (IL-18) release from macrophages by inhibiting caspase-1 (IL-lbeta-converting enzyme). J Immunol 161:4122–4128

    PubMed  CAS  Google Scholar 

  • Kim YM, Bombeck CA, Billiar TR (1999) Nitric Oxide as a Bifunctional Regulator of Apoptosis. Circ Res (In press)

    Google Scholar 

  • Kiss J, Lamarque D, Delchier JC, Whittle BJ (1997) Time-dependent actions of nitric oxide synthase inhibition on colonic inflammation induced by trinitrobenzene sulphonic acid in rats. Eur J Pharmacol 336:219–224

    PubMed  CAS  Google Scholar 

  • Konttinen YT, Platts LA, Tuominen S, Eklund KK, Santavirta N, Tornwall J, Sorsa T, Hukkanen M, Polak JM (1997) Role of nitric oxide in Sjogren’s syndrome. Arthritis Rheum 40:875–883

    PubMed  CAS  Google Scholar 

  • Kooy NW, Royall JA, Ye YZ, Kelly DR, Beckman JS (1995) Evidence for in vivo peroxynitrite production in human acute lung injury. Am J Respir Crit Care Med 151:1250–1254

    PubMed  CAS  Google Scholar 

  • Kooy NW, Lewis SJ, Royall JA, Ye YZ, Kelly DR, Beckman JS (1997) Extensive tyrosine nitration in human myocardial inflammation: evidence for the presence of peroxynitrite. Crit Care Med 25:812–819

    PubMed  CAS  Google Scholar 

  • Kosonen O, Kankaanranta H, Lahde M, Vuorinen P, Ylitalo P, Moilanen E (1998a) Nitric oxide-releasing oxatriazole derivatives inhibit human lymphocyte proliferation by a cyclic GMP-independent mechanism. J Pharmacol Exp Ther 286:215–220

    PubMed  CAS  Google Scholar 

  • Kosonen O, Kankaanranta H, Malo-Ranta U, Ristimaki A, Moilanen E (1998b) Inhibition by nitric oxide-releasing compounds of prostacyclin production in human endothelial cells. Br J Pharmacol 125:247–254

    PubMed  CAS  Google Scholar 

  • Kröncke KD, Fehsel K, Kolb-Bachofen V (1998) Inducible nitric oxide synthase in human diseases. Clin Exp Immunol 113:147–156

    PubMed  Google Scholar 

  • Kubes P, Suzuki M, Granger DN (1991) Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci USA 88:4651–4655

    PubMed  CAS  Google Scholar 

  • Kuhn A, Fehsel K, Lehmann P, Krutmann J, Ruzicka T, Kolb-Bachofen V (1998) Aberrant timing in epidermal expression of inducible nitric oxide synthase after UV irradiation in cutaneous lupus erythematosus. J Invest Dermatol 111:149–153

    PubMed  CAS  Google Scholar 

  • Lafond-Walker A, Chen CL, Augustine S, Wu TC, Hruban RH, Lowenstein CJ (1997a) Inducible nitric oxide synthase expression in coronary arteries of transplanted human hearts with accelerated graft arteriosclerosis. Am J Pathol 151:919–925

    PubMed  CAS  Google Scholar 

  • Lafond-Walker A, Chen CL, Augustine S, Wu TC, Hruban RH, Lowenstein CJ (1997b) Inducible nitric oxide synthase expression in coronary arteries of transplanted human hearts with accelerated graft arteriosclerosis. Am J Pathol 151:919–925

    PubMed  CAS  Google Scholar 

  • Langrehr JM, Hoffman RA, Lancaster JRJ, Simmons RL (1993) Nitric oxide-a new endogenous immunomodulator. Transplantation 55:1205–1212

    PubMed  CAS  Google Scholar 

  • Laubach VE, Shesely EG, Smithies O, Sherman PA (1995) Mice lacking inducible nitric oxide synthase are not resistant to lipopolysaccharide-induced death. Proc Natl Acad Sci USA 92:10688–10692

    PubMed  CAS  Google Scholar 

  • Leib SL, Kim YS, Black SM, Tureen JH, Tauber MG (1998) Inducible nitric oxide synthase and the effect of aminoguanidine in experimental neonatal meningitis. J Infect Dis 177:692–700

    PubMed  CAS  Google Scholar 

  • Li J, Billiar TR (1999) Determinants of Nitric Oxide Protection and Toxicity in Liver. Am J Physiol (In Press)

    Google Scholar 

  • Liaudet L, Rosselet A, Schaller MD, Markert M, Perret C, Feihl F (1998) Nonselective versus selective inhibition of inducible nitric oxide synthase in experimental endotoxic shock. J Infect Dis 177:127–132

    PubMed  CAS  Google Scholar 

  • Linn SC, Morelli PJ, Edry I, Cottongim SE, Szabo C, Salzman AL (1997) Transcriptional regulation of human inducible nitric oxide synthase gene in an intestinal epithelial cell line. Am J Physiol 272:G1499–G1508

    PubMed  CAS  Google Scholar 

  • Liu S, Adcock IM, Old RW, Barnes PJ, Evans TW (1993) Lipopolysaccharide treatment in vivo induces widespread tissue expression of inducible nitric oxide synthase mRNA. Biochem Biophys Res Commun 196:1208–1213

    PubMed  CAS  Google Scholar 

  • Liu SF, Ye X, Malik AB (1997a) In vivo inhibition of nuclear factor-kappa B activation prevents inducible nitric oxide synthase expression and systemic hypotension in a rat model of septic shock. J Immunol 159:3976–3983

    PubMed  CAS  Google Scholar 

  • Liu P, Hock CE, Nagele R, Wong PY (1997b) Formation of nitric oxide, Superoxide, and peroxynitrite in myocardial ischemia-reperfusion injury in rats. Am J Physiol 272:H2327–H2336

    PubMed  CAS  Google Scholar 

  • Liu P, Yin K, Nagele R, Wong PY (1998) Inhibition of nitric oxide synthase attenuates peroxynitrite generation, but augments neutrophil accumulation in hepatic ischemia-reperfusion in rats. J Pharmacol Exp Ther 284:1139–1146

    PubMed  CAS  Google Scholar 

  • Lundberg JO, Ehren I, Jansson O, Adolfsson J, Lundberg JM, Weitzberg E, Alving K, Wiklund NP (1996) Elevated nitric oxide in the urinary bladder in infectious and noninfectious cystitis. Urology 48:700–702

    PubMed  CAS  Google Scholar 

  • Luoma JS, Stralin P, Marklund SL, Hiltunen TP, Sarkioja T, Yla-Herttuala S (1998) Expression of extracellular SOD and iNOS in macrophages and smooth muscle cells in human and rabbit atherosclerotic lesions: colocalization with epitopes characteristic of oxidized LDL and peroxynitrite-modified proteins. Arterioscler Thromb Vasc Biol 18:157–167

    PubMed  CAS  Google Scholar 

  • Lyons CR (1995) The role of nitric oxide in inflammation. Adv Immunol 60:323–371, 323-371

    PubMed  CAS  Google Scholar 

  • MacMicking JD, Nathan C, Horn G, Chartrain N, Fletcher DS, Trumbauer M, Stevens K, Xie QW, Sokol K, Hutchinson N (1995) Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase. Cell 81:641–650

    PubMed  CAS  Google Scholar 

  • MacMicking JD, North RJ, LaCourse R, Mudgett JS, Shah SK, Nathan CF (1997a) Identification of nitric oxide synthase as a protective locus against tuberculosis. Proc Natl Acad Sci USA 94:5243–5248

    PubMed  CAS  Google Scholar 

  • MacMicking, J, Xie Qw, Nathan C (1997c) Nitric oxide and macrophage function. Annu Rev Immunol 15:323–350

    PubMed  CAS  Google Scholar 

  • Mannick EE, Bravo LE, Zarama G, Realpe JL, Zhang XJ, Ruiz B, Fontham ET, Mera R, Miller MJ, Correa P (1996) Inducible nitric oxide synthase, nitrotyrosine, and apoptosis in Helicobacter pylori gastritis: effect of antibiotics and antioxidants. Cancer Res 56:3238–3243

    PubMed  CAS  Google Scholar 

  • Marietta MA, Yoon PS, Iyengar R, Leaf CD, Wishnok JS (1988) Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate. Biochemistry 27:8706–8711

    Google Scholar 

  • Marotta P, Sautebin L, Di Rosa M (1992) Modulation of the induction of nitric oxide synthase by eicosanoids in the murine macrophage cell line J774. Br J Pharmacol 107:640–641

    PubMed  CAS  Google Scholar 

  • Mayer B, Hemmens B (1997) Biosynthesis and action of nitric oxide in mammalian cells. Trends Biochem Sci 22:477–481

    PubMed  CAS  Google Scholar 

  • McCafferty DM, Mudgett JS, Swain MG, Kubes P (1997) Inducible nitric oxide synthase plays a critical role in resolving intestinal inflammation. Gastroenterology 112:1022–1027

    PubMed  CAS  Google Scholar 

  • McCartney-Francis N, Allen JB, Mizel DE, Albina JE, Xie Qw, Nathan CF, Wahl SM (1993) Suppression of arthritis by an inhibitor of nitric oxide synthase. J Exp Med 178:749–754

    PubMed  CAS  Google Scholar 

  • McDermott CD, Gavita SM, Shennib H, Giaid A (1997) Immunohistochemical localization of nitric oxide synthase and the oxidant peroxynitrite in lung transplant recipients with obliterative bronchiolitis. Transplantation 64:270–274

    PubMed  CAS  Google Scholar 

  • Mclnnes IB, Leung BP, Field M, Wei XQ, Huang FP, Sturrock RD, Kinninmonth A, Weidner J, Mumford R, Liew FY (1996) Production of nitric oxide in the synovial membrane of rheumatoid and osteoarthritis patients. J Exp Med 184:1519–1524

    Google Scholar 

  • Mclnnes IB, Leung B, Wei XQ, Gemmell CC, Liew FY (1998) Septic arthritis following Staphylococcus aureus infection in mice lacking inducible nitric oxide synthase. J Immunol 160:308–315

    Google Scholar 

  • Miesel R, Kurpisz M, Kroger H (1996) Suppression of inflammatory arthritis by simultaneous inhibition of nitric oxide synthase and NADPH oxidase. Free Radic Biol Med 20:75–81

    PubMed  CAS  Google Scholar 

  • Milano S, Arcoleo F, Dieli M, D’Agostino R, D’Agostino P, De Nucci G, Cillari E (1995) Prostaglandin E2 regulates inducible nitric oxide synthase in the murine macrophage cell line J774. Prostaglandins 49:105–115

    PubMed  CAS  Google Scholar 

  • Miller MJ, Thompson JH, Zhang XJ, Sadowska-Krowicka H, Kakkis JL, Munshi UK, Sandoval M, Rossi JL, Eloby-Childress S, Beckman JS (1995) Role of inducible nitric oxide synthase expression and peroxynitrite formation in guinea pig ileitis. Gastroenterology 109:1475–1483

    PubMed  CAS  Google Scholar 

  • Moncada S (1997) Nitric oxide in the vasculature: physiology and pathophysiology. Ann NY Acad Sci 811:60–67

    PubMed  CAS  Google Scholar 

  • Moncada S, Higgs EA (1993) The L-arginine-nitric oxide pathway. N Engl J Med 329:2002–2012

    PubMed  CAS  Google Scholar 

  • Moncada S, Palmer RMJ, Higgs EA (1991) Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 43:109–142

    PubMed  CAS  Google Scholar 

  • Mosmann TR, Sad S (1996) The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today 17:138–146

    PubMed  CAS  Google Scholar 

  • Mourelle M, Casellas F, Guarner F, Salas A, Riveros-Moreno V, Moncada S, Malagelada JR (1995) Induction of nitric oxide synthase in colonic smooth muscle from patients with toxic megacolon. Gastroenterology 109:1497–1502

    PubMed  CAS  Google Scholar 

  • Mourelle M, Vilaseca J, Guarner F, Salas A, Malagelada JR (1996) Toxic dilatation of colon in a rat model of colitis is linked to an inducible form of nitric oxide synthase. Am J Physiol 270:G425–G430

    PubMed  CAS  Google Scholar 

  • Munder M, Eichmann K, Modolell M (1998) Alternative metabolic states in murine macrophages reflected by the nitric oxide synthase/arginase balance: competitive regulation by CD4+ T cells correlates with Thl/Th2 phenotype. J Immunol 160:5347–5354

    PubMed  CAS  Google Scholar 

  • Nathan C (1987) Secretory products of macrophages. J Clin Invest 79:319–326

    PubMed  CAS  Google Scholar 

  • Nathan C (1997) Inducible nitric oxide synthase: what difference does it make? J Clin Invest 100:2417–2423

    PubMed  CAS  Google Scholar 

  • Nathan C, Xie QW (1994) Nitric oxide synthases: roles, tolls, and controls. Cell 78:915–918

    PubMed  CAS  Google Scholar 

  • Nozaki Y, Hasegawa Y, Takeuchi A, Fan ZH, Isobe KI, Nakashima I, Shimokata K (1997) Nitric oxide as an inflammatory mediator of radiation pneumonitis in rats. Am J Physiol 272:L651–L658

    PubMed  CAS  Google Scholar 

  • Numata M, Suzuki S, Miyazawa N, Miyashita A, Nagashima Y, Inoue S, Kaneko T, Okubo T (1998) Inhibition of inducible nitric oxide synthase prevents LPS-induced acute lung injury in dogs. J Immunol 160:3031–3037

    PubMed  CAS  Google Scholar 

  • Nüssler AK, Billiar TR (1993) Inflammation, immunoregulation, and inducible nitric oxide synthase. J Leukoc Biol 54:171–178

    PubMed  Google Scholar 

  • Oates JC, Ruiz P, Alexander A, Pippen AM, Gilkeson GS (1997) Effect of late modulation of nitric oxide production on murine lupus. Clin Immunol Immunopathol 83:86–92

    PubMed  CAS  Google Scholar 

  • Olee T, Hashimoto S, Quach J, Lotz M (1999) IL-18 is produced by articular chondrocytes and induces proinflammatory and catabolic responses. J Immunol 162:1096–1100

    PubMed  CAS  Google Scholar 

  • Ou J, Carlos TM, Watkins SC, Saavedra JE, Keefer LK, Kim YM, Harbrecht BG, Billiar TR (1997) Differential effects of nonselective nitric oxide synthase (NOS) and selective inducible NOS inhibition on hepatic necrosis, apoptosis, ICAM-1 expression, and neutrophil accumulation during endotoxemia. Nitric Oxide 1:404–416

    PubMed  CAS  Google Scholar 

  • Oyama J, Shimokawa H, Momii H, Cheng X, Fukuyama N, Arai Y, Egashira K, Nakazawa H, Takeshita A (1998) Role of nitric oxide and peroxynitrite in the cytokine-induced sustained myocardial dysfunction in dogs in vivo. J Clin Invest 101:2207–2214

    PubMed  CAS  Google Scholar 

  • Palmer RMJ, Ferrige AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327:524–526

    PubMed  CAS  Google Scholar 

  • Pang L, Hoult JRS (1996) Induction of cyclooxygenase and nitric oxide synthase in endotoxin-activated J774 macrophages is differentially regulated by indomethacin: Enhanced cyclooxygenase-2 protein expression but reduction of inducible nitric oxde synthase. Eur J Pharmacol 317:151–155

    PubMed  CAS  Google Scholar 

  • Park JH, Chang SH, Lee KM, Shin SH (1996) Protective effect of nitric oxide in an endotoxin-induced septic shock. Am J Surg 171:340–345

    PubMed  CAS  Google Scholar 

  • Parrillo JE (1993) Pathogenetic mechanisms of septic shock. N Engl J Med 328:1471–1477

    PubMed  CAS  Google Scholar 

  • Pender BS, Chen H, Ashton S, Wise WC, Zingarelli B, Cusumano V, Cook JA (1996) Transforming growth factor beta 1 alters rat peritoneal macrophage mediator production and improves survival during endotoxic shock. Eur Cytokine Netw 7:137–142

    PubMed  CAS  Google Scholar 

  • Peng HB, Spiecker M, Liao JK (1998) Inducible nitric oxide: an autoregulatory feedback inhibitor of vascular inflammation. J Immunol 161:1970–1976

    PubMed  CAS  Google Scholar 

  • Perrella MA, Hsieh CM, Lee WS, Shieh S, Tsai JC, Patterson C, Lowenstein CJ, Long NC, Haber E, Shore S, Lee ME (1996) Arrest of endotoxin-induced hypotension by transforming growth factor betal. Proc Natl Acad Sci USA 93:2054–2059

    PubMed  CAS  Google Scholar 

  • Petros A, Bennett D, Vallance P (1991) Effect of nitric oxide synthase inhibitors on hypotension in patients with septic shock. Lancet 338:1557–1558

    PubMed  CAS  Google Scholar 

  • Pou S, Pou WS, Bredt DS, Snyder SH, Rosen GM (1992) Generation of Superoxide by purified brain nitric oxide synthase. J Biol Chem 267:24173–24176

    PubMed  CAS  Google Scholar 

  • Ribbons KA, Currie MG, Connor JR, Manning PT, Allen PC, Didier P, Ratterree MS, Clark DA, Miller MJ (1997) The effect of inhibitors of inducible nitric oxide synthase on chronic colitis in the rhesus monkey. J Pharmacol Exp Ther 280:1008–1015

    PubMed  CAS  Google Scholar 

  • Ridger VC, Pettipher ER, Bryant CE, Brain SD (1997) Effect of the inducible nitric oxide synthase inhibitors aminoguanidine and L-N6-(1-iminoethyl)lysine on zymosan-induced plasma extravasation in rat skin. J Immunol 159:383–390

    PubMed  CAS  Google Scholar 

  • Ross R (1999) Atherosclerosis-an inflammatory disease. N Engl J Med 340:115–126

    PubMed  CAS  Google Scholar 

  • Rowe A, Farrell AM, Bunker CB (1997) Constitutive endothelial and inducible nitric oxide synthase in inflammatory dermatoses. Br J Dermatol 136:18–23

    PubMed  CAS  Google Scholar 

  • Ryffel B (1997) Impact of knockout mice in toxicology. Crit Rev Toxicol 27:135–154

    PubMed  CAS  Google Scholar 

  • Sadowska-Krowicka H, Mannick EE, Oliver PD, Sandoval M, Zhang XJ, Eloby-Childess S, Clark DA, Miller MJ (1998) Genistein and gut inflammation: role of nitric oxide. Proc Soc Exp Biol Med 217:351–357

    PubMed  CAS  Google Scholar 

  • Saleh D, Barnes PJ, Giaid A (1997) Increased production of the potent oxidant peroxynitrite in the lungs of patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 155:1763–1769

    PubMed  CAS  Google Scholar 

  • Saleh D, Ernst P, Lim S, Barnes PJ, Giaid A (1998) Increased formation of the potent oxidant peroxynitrite in the airways of asthmatic patients is associated with induction of nitric oxide synthase: effect of inhaled glucocorticoid. FASEB J 12:929–937

    PubMed  CAS  Google Scholar 

  • Salvemini D, Misko TP, Masferrer JL, Seibert K, Currie MG, Needleman P (1993) Nitric oxide activates cyclooxygenase enzymes. Proc Natl Acad Sci USA 90:7240–7244

    PubMed  CAS  Google Scholar 

  • Salvemini D, Seibert K, Marino MH (1996a) PG release, as a consequence of NO-driven COX activation, contributes to the proinflammatory effects of NO. Drugs News Perspect 4:204–219

    Google Scholar 

  • Salvemini D, Wang ZQ, Bourdon DM, Stern MK, Currie MG, Manning PT (1996b) Evidence of peroxynitrite involvement in the carrageenan-induced rat paw edema. Eur J Pharmacol 303:217–220

    PubMed  CAS  Google Scholar 

  • Salvemini D, Wang ZQ, Wyatt PS, Bourdon DM, Marino MH, Manning PT, Currie MG (1996c) Nitric oxide: a key mediator in the early and late phase of carrageenaninduced rat paw inflammation. Br J Pharmacol 118:829–838

    PubMed  CAS  Google Scholar 

  • Samlowski WE, Yim CY, McGregor JR (1998) Nitric oxide exposure inhibits induction of lymphokine-activated killer cells by inducing precursor apoptosis. Nitric Oxide 2:45–56

    PubMed  CAS  Google Scholar 

  • Santos LL, Morand EF, Yang Y, Hutchinson P, Holdsworth SR (1997) Suppression of adjuvant arthritis and synovial macrophage inducible nitric oxide by N-iminoethyl-L-ornithine, a nitric oxide synthase inhibitor. Inflammation 21:299–311

    PubMed  CAS  Google Scholar 

  • Satoi H, Oka N, Kawasaki T, Miyamoto K, Akiguchi I, Kimura J (1998) Mechanisms of tissue injury in vasculitic neuropathies. Neurology 50:492–496

    PubMed  CAS  Google Scholar 

  • Schuberth HJ, Hendricks A, Leibold W (1998) There is no regulatory role for induced nitric oxide in the regulation of the in vitro proliferative response of bovine mononuclear cells to mitogens, alloantigens or superantigens. Immunobiology 198:439–450

    PubMed  CAS  Google Scholar 

  • Shears LL, Kawaharada N, Tzeng E, Billiar TR, Watkins SC, Kovesdi I, Lizonova A, Pham SM (1997) Inducible nitric oxide synthase suppresses the development of allograft arteriosclerosis. J Clin Invest 100:2035–2042

    PubMed  CAS  Google Scholar 

  • Shin T, Tanuma N, Kim S, Jin J, Moon C, Kim K, Kohyama K, Matsumoto Y, Hyun B (1998) An inhibitor of inducible nitric oxide synthase ameliorates experimental autoimmune myocarditis in Lewis rats. J Neuroimmunol 92:133–138

    PubMed  CAS  Google Scholar 

  • Shoker AS, Yang H, Murabit MA, Jamil H, al-Ghoul A, Okasha K (1997) Analysis of the in vitro effect of exogenous nitric oxide on human lymphocytes. Mol Cell Biochem 171:75–83

    PubMed  CAS  Google Scholar 

  • Singer II, Kawka DW, Scott S, Weidner JR, Mumford RA, Riehl TE, Stenson WF (1996) Expression of inducible nitric oxide synthase and nitrotyrosine in colonic epithelium in inflammatory bowel disease. Gastroenterology 111:871–885

    PubMed  CAS  Google Scholar 

  • Souza-Fiho MV, Lima MV, Pompeu MM, Ballejo G, Cunha FQ, Ribeiro RD (1997) Involvement of nitric oxide in the pathogenesis of cyclophosphamide-induced hemorrhagic cystitis. Am J Pathol 150:247–256

    PubMed  CAS  Google Scholar 

  • Spiecker M, Peng HB, Liao JK (1997) Inhibition of endothelial vascular cell adhesion molecule-1 expression by nitric oxide involves the induction and nuclear translocation of IκBα. J Biol Chem 272:30969–30974

    PubMed  CAS  Google Scholar 

  • Spink J, Cohen J, Evans TJ (1995) The cytokine responsive vascular smooth muscle cell enhancer of inducible nitric oxide synthase. Activation by nuclear factor-κB. J Biol Chem 270:29541–29547

    PubMed  CAS  Google Scholar 

  • Stadler J, Stefanovic-Racic M, Billiar TR, Curran RD, Mclntyre LA, Georgescu HI, Simmons RL, Evans CH (1991) Articular chondrocytes synthesize nitric oxide in response to cytokines and lipopolysaccharide. J Immunol 147:3915–3920

    PubMed  CAS  Google Scholar 

  • Stadler J, Harbrecht BG, Di Silvio M, Curran RD, Jordan ML, Simmons RL, Billiar TR (1993) Endogenous nitric oxide inhibits the synthesis of cyclooxygenase products and interleukin-6 by rat Kupffer cells. J Leukoc Biol 53:165–172

    PubMed  CAS  Google Scholar 

  • Stuehr DJ, Marietta MA (1985) Mammalian nitrate biosynthesis: mouse macrophages produce nitrite and nitrate in response to Escherichia coli lipopolysaccharide. Proc Natl Acad Sci USA 82:7738–7742

    PubMed  CAS  Google Scholar 

  • Stuehr DJ, Nathan CF (1989) Nitric oxide, a macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells. J Exp Med 169:1543–1545

    PubMed  CAS  Google Scholar 

  • Swierkosz TA, Mitchell JA, Warner TD, Botting RM, Vane JR (1995) Co-induction of nitric oxide synthase and cyclo-oxygenase: interactions between nitric oxide and prostanoids. Br J Pharmacol 114:1335–1342

    PubMed  CAS  Google Scholar 

  • Szabo C (1998) Role of poly(ADP-ribose)synthetase in inflammation. Eur J Pharmacol 350:1–19

    PubMed  CAS  Google Scholar 

  • Szabo C, Dawson VL (1998) Role of poly(ADP-ribose) synthetase in inflammation and ischaemia reperfusion. Trends Pharmacol Sci 19:287–298

    PubMed  CAS  Google Scholar 

  • Szabo C, Southan GJ, Thiemermann C (1994) Beneficial effects and improved survival in rodent models of septic shock with S-methylisothiourea sulfate, a potent and selective inhibitor of inducible nitric oxide synthase. Proc Natl Acad Sci USA 91:12472–12476

    PubMed  CAS  Google Scholar 

  • Szabo C, Salzman AL, Ischiropoulos H (1995) Endotoxin triggers the expression of an inducible isoform of nitric oxide synthase and the formation of peroxynitrite in the rat aorta in vivo. FEBS Lett 363:235–238

    PubMed  CAS  Google Scholar 

  • Szabo C, Lim LH, Cuzzocrea S, Getting SJ, Zingarelli B, Flower RJ, Salzman AL, Perretti M (1997) Inhibition of poly (ADP-ribose) synthetase attenuates neutrophil recruitment and exerts antiinflammatory effects. J Exp Med 186:1041–1049

    PubMed  CAS  Google Scholar 

  • Szabolcs MJ, Ravalli S, Minanov O, Sciacca RR, Michler RE, Cannon PJ (1998) Apoptosis and increased expression of inducible nitric oxide synthase in human allograft rejection. Transplantation 65:804–812

    PubMed  CAS  Google Scholar 

  • Takeichi O, Saito I, Hayashi M, Tsurumachi T, Saito T (1998) Production of humaninducible nitric oxide synthase in radicular cysts. J Endod 24:157–160

    PubMed  CAS  Google Scholar 

  • Tanaka S, Kamiike W, Ito T, Uchikoshi F, Matsuda H, Nozawa M, Kumura E, Shiga T, Kosaka H (1995) Generation of nitric oxide as a rejection marker in rat pancreas transplantation. Transplantation 60:713–717

    PubMed  CAS  Google Scholar 

  • Tarrant TK, Silver PB, Wahlsten JL, Rizzo LV, Chan CC, Wiggert B, Caspi RR (1999) Interleukin 12 protects from a T-helper type-1-mediated autoimmune disease, experimental autoimmune uveitis, through a mechanism involving interferon γ, nitric oxide, and apoptosis. J Exp Med 189:219–230

    PubMed  CAS  Google Scholar 

  • Taylor BS, de Vera ME, Ganster RW, Wang Q, Shapiro RA, Morris SMJ, Billiar TR, Geller DA (1998) Multiple NF-κB enhancer elements regulate cytokine induction of the human inducible nitric oxide synthase gene. J Biol Chem 273:15148–15156

    PubMed  CAS  Google Scholar 

  • Taylor-Robinson AW (1997) Counter-regulation of T-helper-1 cell proliferation by nitric oxide and interleukin-2. Biochem Biophys Res Commun 233:14–19

    PubMed  CAS  Google Scholar 

  • Ter Steege J, Buurman W, Arends JW, Forget P (1997) Presence of inducible nitric oxide synthase, nitrotyrosine, CD68, and CD14 in the small intestine in celiac disease. Lab Invest 77:29–36

    PubMed  CAS  Google Scholar 

  • Tracey WR, Xue C, Klinghofer V, Barlow J, Pollock JS, Forstermann U, Johns RA (1994) Immunochemical detection of inducible NO synthase in human lung. Am J Physiol 266:L722–L727

    PubMed  CAS  Google Scholar 

  • Trepicchio WL, Bozza M, Pedneault G, Dorner AJ (1996) Recombinant human IL-11 attenuates the inflammatory response through down-regulation of proinflammatory cytokine release and nitric oxide production. J Immunol 157:3627–3634

    PubMed  CAS  Google Scholar 

  • Trowbridge HO, Emling RC (1997) Inflammation: a review of the process. Quintessence, Chicago

    Google Scholar 

  • Tsuji M, Dimov VB, Yoshida T (1995) In vivo expression of monokine and inducible nitric oxide synthase in experimentally induced pulmonary granulomatous inflammation. Evidence for sequential production of interleukin-1, inducible nitric oxide synthase, and tumor necrosis factor. Am J Pathol 147:1001–1015

    PubMed  CAS  Google Scholar 

  • Van de Loo FA, Arntz OJ, van Enckevort FH, van Lent PL, van den Berg WB (1998) Reduced cartilage proteoglycan loss during zymosan-induced gonarthritis in NOS2-deficient mice and in anti-interleukin-1-treated wild-type mice with unabated joint inflammation. Arthritis Rheum 41:634–646

    PubMed  Google Scholar 

  • Van der Veen RC, Hinton DR, Incardonna F, Hofman FM (1997) Extensive peroxynitrite activity during progressive stages of central nervous system inflammation. J Neuroimmunol 77:1–7

    PubMed  Google Scholar 

  • Vara E, Arias-Diaz J, Garcia C, Hernandez J, Garcia-Carreras C, Cuadrado A, Balibrea JL (1995) Production of TNF alpha, IL-1, IL-6 and nitric oxide by isolated human islets. Transplant Proc 27:3367–3371

    PubMed  CAS  Google Scholar 

  • Vodovotz Y, Bogdan C, Paik J, Xie QW, Nathan C (1993) Mechanisms of suppression of macrophage nitric oxide release by transforming growth factor beta. J Exp Med 178:605–613

    PubMed  CAS  Google Scholar 

  • Vodovotz Y, Geiser AG, Chesler L, Letterio JJ, Campbell A, Lucia MS, Sporn MB, Roberts AB (1996a) Spontaneously increased production of nitric oxide and aberrant expression of the inducible nitric oxide synthase in vivo in the transforming growth factor beta 1 null mouse. J Exp Med 183:2337–2342

    PubMed  CAS  Google Scholar 

  • Vodovotz Y, Letterio JJ, Geiser AG, Chesler L, Roberts AB, Sparrow J (1996b) Control of nitric oxide production by endogenous TGF-betal and systemic nitric oxide in retinal pigment epithelial cells and peritoneal macrophages. J Leukoc Biol 60:261–270

    PubMed  CAS  Google Scholar 

  • Vodovotz Y, Kopp JB, Takeguchi H, Shrivastav S, Coffin D, Lucia MS, Mitchell JB, Webber R, Letterio J, Wink D, Roberts AB (1998) Increased mortality, blunted production of nitric oxide, and increased production of TNF-α in endotoxemic TGF-β1 transgenic mice. J Leukoc Biol 63:31–39

    PubMed  CAS  Google Scholar 

  • Vos TA, Gouw AS, Klok PA, Havinga R, van Goor H, Huitema S, Roelofsen H, Kuipers F, Jansen PL, Moshage H (1997) Differential effects of nitric oxide synthase inhibitors on endotoxin-induced liver damage in rats. Gastroenterology 113:1323–1333

    PubMed  CAS  Google Scholar 

  • Wagner DA, Young VR, Tannenbaum SR (1983) Mammalian nitrate biosynthesis: Incorporation of15NH3 into nitrate is enhanced by endotoxin treatment. Proc Natl Acad Sci USA 80:4518–4521

    PubMed  CAS  Google Scholar 

  • Wang JS, Tseng HH, Shih DF, Jou HS, Ger LP (1997) Expression of inducible nitric oxide synthase and apoptosis in human lupus nephritis. Nephron 77:404–411

    PubMed  CAS  Google Scholar 

  • Wang R, Ghahary A, Shen YJ, Scott PG, Tredget EE (1996a) Human dermal fibroblasts produce nitric oxide and express both constitutive and inducible nitric oxide synthase isoforms. J Invest Dermatol 106:419–427

    PubMed  CAS  Google Scholar 

  • Wang ZY, Alm P, Hakanson R (1996b) The contribution of nitric oxide to endotoxininduced ocular inflammation: interaction with sensory nerve fibres. Br J Pharmacol 118:1537–1543

    PubMed  CAS  Google Scholar 

  • Watkins SC, Macaulay W, Turner D, Kang R, Rubash HE, Evans CH (1997) Identification of inducible nitric oxide synthase in human macrophages surrounding loosened hip prostheses. Am J Pathol 150:1199–1206

    PubMed  CAS  Google Scholar 

  • Wei XQ, Charles IG, Smith A, Ure J, Feng GJ, Huang FP, Xu D, Muller W, Moncada S, Liew FY (1995) Altered immune responses in mice lacking inducible nitric oxide synthase. Nature 375:408–411

    PubMed  CAS  Google Scholar 

  • Werner J, Rivera J, Fernandez-del CC, Lewandrowski K, Adrie C, Rattner DW, Warshaw AL (1997) Differing roles of nitric oxide in the pathogenesis of acute edematous versus necrotizing pancreatitis. Surgery 121:23–30

    PubMed  CAS  Google Scholar 

  • Whittle BJ (1997) Nitric oxide-a mediator of inflammation or mucosal defence. Eur J Gastroenterol Hepatol 9:1026–1032

    PubMed  CAS  Google Scholar 

  • Wigand R, Meyer J, Busse R, Hecker M (1997) Increased serum N G-hydroxy-L-arginine in patients with rheumatoid arthritis and systemic lupus erythematosus as an index of an increased nitric oxide synthase activity. Ann Rheum Dis 56:330–332

    PubMed  CAS  Google Scholar 

  • Wink DA, Hanbauer I, Grisham MB, Laval F, Nims RW, Laval J, Cook J, Pacelli R, Liebmann J, Krishna M, Ford PC, Mitchell JB (1996) Chemical biology of nitric oxide: regulation and protective and toxic mechanisms. Curr Top Cell Regul 34:159–87, 159-187

    PubMed  CAS  Google Scholar 

  • Winlaw DS, Schyvens CG, Smythe GA, Du ZY, Rainer SP, Lord RS, Spratt PM, Macdonald PS (1995) Selective inhibition of nitric oxide production during cardiac allograft rejection causes a small increase in graft survival. Transplantation 60:77–82

    PubMed  CAS  Google Scholar 

  • Wizemann TM, Gardner CR, Laskin JD, Quinones S, Durham SK, Goller NL, Ohnishi ST, Laskin DL (1994) Production of nitric oxide and peroxynitrite in the lung during acute endotoxemia. J Leukoc Biol 56:759–768

    PubMed  CAS  Google Scholar 

  • Wolkow PP (1998) Involvement and dual effects of nitric oxide in septic shock. Inflamm Res 47:152–166

    PubMed  CAS  Google Scholar 

  • Wong HR, Finder JD, Wasserloos K, Lowenstein CJ, Geller DA, Billiar TR, Pitt BR, Davies P (1996) Transcriptional regulation of iNOS by IL-1 beta in cultured rat pulmonary artery smooth muscle cells. Am J Physiol 271:L166–L171

    PubMed  CAS  Google Scholar 

  • Wu CC, Chen SJ, Szabo C, Thiemermann C, Vane JR (1995) Aminoguanidine attenuates the delayed circulatory failure and improves survival in rodent models of endotoxic shock. Br J Pharmacol 114:1666–1672

    PubMed  CAS  Google Scholar 

  • Xie QW, Kashiwabara Y, Nathan C (1994) Role of transcription factor NF-κB/Rel in induction of nitric oxide synthase. J Biol Chem 269:4705–4708

    PubMed  CAS  Google Scholar 

  • Xiong Y, Karupiah G, Hogan SP, Foster PS, Ramsay AJ (1999) Inhibition of allergic airway inflammation in mice lacking nitric oxide synthase 2. J Immunol 162:445–452

    PubMed  CAS  Google Scholar 

  • Yamamoto T, Katayama I, Nishioka K (1998) Nitric oxide production and inducible nitric oxide synthase expression in systemic sclerosis. J Rheumatol 25:314–317

    PubMed  CAS  Google Scholar 

  • Yamasaki K, Edington HD, McClosky C, Tzeng E, Lizonova A, Kovesdi I, Steed DL, Billiar TR (1998) Reversal of impaired wound repair in iNOS-deficient mice by topical adenoviral-mediated iNOS gene transfer. J Clin Invest 101:967–971

    PubMed  CAS  Google Scholar 

  • Zamora R, Bult H, Herman AG (1998) The role of prostaglandin E2 and nitric oxide in cell death in J774 murine macrophages. Eur J Pharmacol 349:307–315 Zhao W, Tilton RG, Corbett JA, McDaniel ML, Misko TP, Williamson JR, Cross AH

    PubMed  CAS  Google Scholar 

  • Hickey WF (1996) Experimental allergic encephalomyelitis in the rat is inhibited by aminoguanidine, an inhibitor of nitric oxide synthase. J Neuroimmunol 64:123–133

    PubMed  Google Scholar 

  • Zielasek J, Jung S, Gold R, Liew FY, Toyka KV, Hartung HP (1995) Administration of nitric oxide synthase inhibitors in experimental autoimmune neuritis and experimental autoimmune encephalomyelitis. J Neuroimmunol 58:81–88

    PubMed  CAS  Google Scholar 

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Authors
  1. R. Zamora
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  2. T. R. Billiar
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Editors and Affiliations

  1. Department of Pharmacology and Toxicology, Karl-Franzens-University of Graz, Universitätsplatz 2, 8010, Graz, Austria

    Bernd Mayer

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© 2000 Springer-Verlag Berlin Heidelberg

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Zamora, R., Billiar, T.R. (2000). Nitric Oxide: A True Inflammatory Mediator. In: Mayer, B. (eds) Nitric Oxide. Handbook of Experimental Pharmacology, vol 143. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-57077-3_20

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  • DOI: https://doi.org/10.1007/978-3-642-57077-3_20

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-63026-2

  • Online ISBN: 978-3-642-57077-3

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