Amino Acids

, Volume 35, Issue 2, pp 397–402 | Cite as

Heme oxygenase-1 participates in the anti-inflammatory activity of taurine chloramine

  • B. Muż
  • E. Kontny
  • J. Marcinkiewicz
  • W. Maśliński


Interleukin-6 (IL-6) and interleukin-8 (IL-8) are implicated in the pathogenesis of rheumatic diseases. In affected joints fibroblast-like synoviocytes (FLS) are the major source of these pro-inflammatory cytokines. We have previously found that production of both cytokines is inhibited in vitro by taurine chloramine (Tau-Cl). Heme oxygenase (HO-1) activity was also reported to restrict synthesis of various inflammatory mediators, including IL-6 and IL-8. The aim of present study was to investigate whether this enzyme activity is implicated in the mechanism of Tau-Cl suppressive effect. We have shown that in rheumatoid FLS both hemin (known HO-1 inducer) and Tau-Cl significantly up-regulate HO-1 expression at the mRNA and protein levels and simultaneously inhibit IL-1β-triggered production of pro-inflammatory cytokines. However, the inhibitory potency of these compounds differs, because hemin is more potent inhibitor of IL-8 than IL-6 production, while Tau-Cl exerts opposite effect. Importantly, pretreatment of the cells with HO-1 inhibitor completely reverses the inhibitory effect of hemin on both cytokines production. However, in Tau-Cl treated cells this inhibitor fully restores only IL-8 secretion but has weaker effect on IL-6 response. Thus, the present results: (i) support HO-1 activity to be relevant to negatively control production of pro-inflammatory cytokines, and (ii) underline implication of HO-1 in mediating Tau-Cl inhibitory action.

Keywords: Interleukins (IL) – Fibroblast-like synoviocytes (FLS) – Rheumatoid arthritis (RA) – Heme oxygenase-1 (HO-1) – Taurine chloramine (Tau-Cl) 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alam, J, Cook, JL 2007How many transcription factors does it take to turn on the heme oxygenase-1 gene?Am J Respir Cell Mol Biol36166174PubMedCrossRefGoogle Scholar
  2. Alcaraz, MJ, Habib, A, Lebret, M, Creminon, C, Levy-Toledano, S, Maclouf, J 2000Enhanced expression of haem oxygenase-1 by nitric oxide and antiinflammatory drugs in NIH 3T3 fibroblastsBr J Pharmacol1305764PubMedCrossRefGoogle Scholar
  3. Bonnet, CS, Walsh, DA 2005Osteoarthritis, angiogenesis and inflammationRheumatology (Oxford)44716CrossRefGoogle Scholar
  4. Cecil, DL, Rose, DM, Terkeltaub, R, Liu-Bryan, R 2005Role of interleukin-8 in PiT-1 expression and CXCR1-mediated inorganic phosphate uptake in chondrocytesArthritis Rheum52144154PubMedCrossRefGoogle Scholar
  5. Dawn, B, Bolli, R 2005HO-1 induction by HIF-1: a new mechanism for delayed cardioprotection?Am J Physiol Heart Circ Physiol289H522H524PubMedCrossRefGoogle Scholar
  6. Gottardi, W, Nagl, M 2002Chemical properties of N-chlorotaurine sodium, a key compound in the human defence systemArch Pharm (Weinheim)335411421CrossRefGoogle Scholar
  7. Ho, FM, Kang, HC, Lee, ST, Chao, Y, Chen, YC, Huang, LJ, Lin, WW 2007The anti-inflammatory actions of LCY-2-CHO, a carbazole analogue, in vascular smooth muscle cellsBiochem Pharmacol74298308PubMedCrossRefGoogle Scholar
  8. Huber, LC, Distler, O, Tarner, I, Gay, RE, Gay, S, Pap, T 2006Synovial fibroblasts: key players in rheumatoid arthritisRheumatology (Oxford)45669675CrossRefGoogle Scholar
  9. Jun, CD, Kim, Y, Choi, EY, Kim, M, Park, B, Youn, B, Yu, K, Choi, KS, Yoon, KH, Choi, SC, Lee, MS, Park, KI, Choi, M, Chung, Y, Oh, J 2006Gliotoxin reduces the severity of trinitrobenzene sulfonic acid-induced colitis in mice: evidence of the connection between heme oxygenase-1 and the nuclear factor-kappaB pathway in vitro and in vivoInflamm Bowel Dis12619629PubMedCrossRefGoogle Scholar
  10. Kataoka, K, Handa, H, Nishizawa, M 2001Induction of cellular antioxidative stress genes through heterodimeric transcription factor Nrf2/small Maf by antirheumatic gold(I) compoundsJ Biol Chem2763407434081PubMedCrossRefGoogle Scholar
  11. Kim, C, Choi, HS, Kim, JW 2006Taurine chloramine inhibits the production of nitric oxide and superoxide anion by modulating specific mitogen-activated protein kinasesAdv Exp Med Biol583493498PubMedCrossRefGoogle Scholar
  12. Kim, KS, Park, EK, Ju, SM, Jung, HS, Bang, JS, Kim, C, Lee, YA, Hong, SJ, Lee, SH, Yang, HI, Yoo, MC 2007Taurine chloramine differentially inhibits matrix metalloproteinase 1 and 13 synthesis in interleukin-1beta-stimulated fibroblast-like synoviocytesArthritis Res Ther9R80PubMedCrossRefGoogle Scholar
  13. Kirino, Y, Takeno, M, Murakami, S, Kobayashi, M, Kobayashi, H, Miura, K, Ideguchi, H, Ohno, S, Ueda, A, Ishigatsubo, Y 2007Tumor necrosis factor alpha acceleration of inflammatory responses by down-regulating heme oxygenase 1 in human peripheral monocytesArthritis Rheum56464475PubMedCrossRefGoogle Scholar
  14. Kirkby, KA, Adin, CA 2006Products of heme oxygenase and their potential therapeutic applicationsAm J Physiol Renal Physiol290F563F571PubMedCrossRefGoogle Scholar
  15. Kobayashi, H, Takeno, M, Saito, T, Takeda, Y, Kirino, Y, Noyori, K, Hayashi, T, Ueda, A, Ishigatsubo, Y 2006Regulatory role of heme oxygenase 1 in inflammation of rheumatoid arthritisArthritis Rheum5411321142PubMedCrossRefGoogle Scholar
  16. Kontny, E, Grabowska, A, Kowalczewski, J, Kurowska, M, Janicka, I, Marcinkiewicz, J, Maslinski, W 1999Taurine chloramine inhibition of cell proliferation and cytokine production by rheumatoid arthritis fibroblast-like synoviocytesArthritis Rheum4225522560PubMedCrossRefGoogle Scholar
  17. Kontny, E, Szczepanska, K, Kowalczewski, J, Kurowska, M, Janicka, I, Marcinkiewicz, J, Maslinski, W 2000The mechanism of taurine chloramine inhibition of cytokine (interleukin-6, interleukin-8) production by rheumatoid arthritis fibroblast-like synoviocytesArthritis Rheum4321692177PubMedCrossRefGoogle Scholar
  18. Kontny, E, Rudnicka, W, Kowalczewski, J, Marcinkiewicz, J, Maslinski, W 2003Selective inhibition of cyclooxygenase 2-generated prostaglandin E2 synthesis in rheumatoid arthritis synoviocytes by taurine chloramineArthritis Rheum4815511555PubMedCrossRefGoogle Scholar
  19. Kontny, E, Chorazy-Massalska, M, Rudnicka, W, Marcinkiewicz, J, Maslinski, W 2006aCytotoxicity of taurine metabolites depends on the cell typeAdv Exp Med Biol583157171CrossRefGoogle Scholar
  20. Kontny, E, Rudnicka, W, Chorazy-Massalska, M, Marcinkiewicz, J, Maslinski, W 2006bTaurine chloramine inhibits proliferation of rheumatoid arthritis synoviocytes by triggering a p53-dependent pathwayInflamm Res55446455CrossRefGoogle Scholar
  21. Kontny, E, Chorazy-Massalska, M, Rudnicka, W, Marcinkiewicz, J, Maslinski, W 2007Comparison of taurine chloramine and taurine bromamine effects on rheumatoid arthritis synoviocytesAmino Acids32447452PubMedCrossRefGoogle Scholar
  22. Mainnemare, A, Megarbane, B, Soueidan, A, Daniel, A, Chapple, IL 2004Hypochlorous acid and taurine-N-monochloramine in periodontal diseasesJ Dent Res83823831PubMedGoogle Scholar
  23. Malemud, CJ 2004Cytokines as therapeutic targets for osteoarthritisBio Drugs182335Google Scholar
  24. Marcinkiewicz, J, Kurnyta, M, Biedron, R, Bobek, M, Kontny, E, Maslinski, W 2006Anti-inflammatory effects of taurine derivatives (taurine chloramine, taurine bromamine, and taurolidine) are mediated by different mechanismsAdv Exp Med Biol583481492PubMedCrossRefGoogle Scholar
  25. McInnes, IB, Schett, G 2007Cytokines in the pathogenesis of rheumatoid arthritisNat Rev Immunol7429442PubMedCrossRefGoogle Scholar
  26. Miyamoto, Y, Kanayama, A, Inoue, J, Konishi, YS, Shimizu, M 2003Taurine is involved in oxidation of IkappaB alpha at Met45: N-halogenated taurine and anti-inflammatory actionAdv Exp Med Biol526373380PubMedGoogle Scholar
  27. Mizuno, K, Toma, T, Tsukiji, H, Okamoto, H, Yamazaki, H, Ohta, K, Kasahara, Y, Koizumi, S, Yachie, A 2005Selective expansion of CD16highCCR2-subpopulation of circulating monocytes with preferential production of haem oxygenase (HO)-1 in response to acute inflammationClin Exp Immunol142461470PubMedGoogle Scholar
  28. Ockaili, R, Natarajan, R, Salloum, F, Fisher, BJ, Jones, D, Fowler, AA,3rd, Kukreja, RC 2005HIF-1 activation attenuates postischemic myocardial injury: role for heme oxygenase-1 in modulating microvascular chemokine generationAm J Physiol Heart Circ Physiol289H542H548PubMedCrossRefGoogle Scholar
  29. Olszanecki, R, Marcinkiewicz, J 2004Taurine chloramine and taurine bromamine induce heme oxygenase-1 in resting and LPS-stimulated J774.2 macrophagesAmino Acids272935PubMedCrossRefGoogle Scholar
  30. Orozco, LD, Kapturczak, MH, Barajas, B, Wang, X, Weinstein, MM, Wong, J, Deshane, J, Bolisetty, S, Shaposhnik, Z, Shih, DM, Agarwal, A, Lusis, AJ, Araujo, JA 2007Heme oxygenase-1 expression in macrophages plays a beneficial role in atherosclerosisCirc Res10017031711PubMedCrossRefGoogle Scholar
  31. Ricchetti, GA, Williams, LM, Foxwell, BM 2004Heme oxygenase 1 expression induced by IL-10 requires STAT-3 and phosphoinositol-3 kinase and is inhibited by lipopolysaccharideJ Leukoc Biol76719726PubMedCrossRefGoogle Scholar
  32. Ryter, SW, Alam, J, Choi, AM 2006Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applicationsPhysiol Rev86583650PubMedCrossRefGoogle Scholar
  33. Shinohara, T, Kaneko, T, Nagashima, Y, Ueda, A, Tagawa, A, Ishigatsubo, Y 2005Adenovirus-mediated transfer and overexpression of heme oxygenase 1 cDNA in lungs attenuates elastase-induced pulmonary emphysema in miceHum Gene Ther16318327PubMedCrossRefGoogle Scholar
  34. Stebulis, JA, Rossetti, RG, Atez, FJ, Zurier, RB 2005Fibroblast-like synovial cells derived from synovial fluidJ Rheumatol32301306PubMedGoogle Scholar
  35. Tron, K, Novosyadlyy, R, Dudas, J, Samoylenko, A, Kietzmann, T, Ramadori, G 2005Upregulation of heme oxygenase-1 gene by turpentine oil-induced localized inflammation: involvement of interleukin-6Lab Invest85376387PubMedCrossRefGoogle Scholar
  36. Tron, K, Samoylenko, A, Musikowski, G, Kobe, F, Immenschuh, S, Schaper, F, Ramadori, G, Kietzmann, T 2006Regulation of rat heme oxygenase-1 expression by interleukin-6 via the Jak/STAT pathway in hepatocytesJ Hepatol457280PubMedCrossRefGoogle Scholar
  37. Wang, CT, Lin, YT, Chiang, BL, Lin, YH, Hou, SM 2006High molecular weight hyaluronic acid down-regulates the gene expression of osteoarthritis-associated cytokines and enzymes in fibroblast-like synoviocytes from patients with early osteoarthritisOsteoarthritis Cartilage1412371247PubMedCrossRefGoogle Scholar
  38. Zwerina, J, Tzima, S, Hayer, S, Redlich, K, Hoffmann, O, Hanslik-Schnabel, B, Smolen, JS, Kollias, G, Schett, G 2005Heme oxygenase 1 (HO-1) regulates osteoclastogenesis and bone resorptionFaseb J1920112013PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • B. Muż
    • 1
  • E. Kontny
    • 1
  • J. Marcinkiewicz
    • 2
  • W. Maśliński
    • 1
  1. 1.Department of Pathophysiology and ImmunologyInstitute of RheumatologyWarsawPoland
  2. 2.Department of ImmunologyMedical College, Jagiellonian UniversityCracowPoland

Personalised recommendations