Skip to main content
SpringerLink
Log in

Anthrax Lethal Factor Represses Glucocorticoid and Progesterone Receptor Activity

  • Chapter
Neural and Neuroendocrine Mechanisms in Host Defense and Autoimmunity

  • 383 Accesses

Abstract

Death from anthrax has been reported to occur from systemic shock. The lethal toxin (LeTx) is the major effector of anthrax mortality. Although the mechanism of entry of this toxin into cells is well understood, its actions once inside the cell are not as well understood. LeTx is known to cleave and inactivate mitogen activated protein kinase kinases (MAPKKs). We have recently shown that LeTx represses the glucocorticoid receptor both in vitro and in vivo. This repression is partial and specific, showing some receptor specificity and some promoter specificity.This toxin does not affect glucocorticoid receptor (GR) ligand binding or DNA binding in an in vitro electrophoretic mobility shift assay using a DNA probe. However, in chromatin immunoprecipitation assays, LeTx prevents GR binding to chromatin. We have suggested that LeTx may function by removing/inactivating one or more of the many cofactors and/or accessory proteins involved in nuclear hormone receptor signaling. Although the precise involvement of this nuclear hormone receptor repression in LeTx toxicity is unknown, examples of blunted hypothalamic-pituitary-adrenal (HPA) axis and glucocorticoid signaling in numerous autoimmune/inflammatory diseases suggest that such repression of critically important receptors could have deleterious effects on health. In addition, removal of endogenous glucocorticoids and treatment with glucocorticoids (in LT-resistant mice) increases susceptibility to LeTx, suggesting that a precise balance of glucocorticoid levels is required for LeTx survival.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abrami, L., Liu, S., Cosson, P., Leppla, S.H., and van der Goot, F.G. (2003). Anthrax toxin triggers endocytosis of its receptor via a lipid raft-mediated clathrin-dependent process. J. Cell. Biol. 160:321–328.

    PubMed  CAS  Google Scholar 

  • Abrami, L., Lindsay, M., Parton, R.G., Leppla, S.H., and van der Goot, F.G. (2004). Membrane insertion of anthrax protective antigen and cytoplasmic delivery of lethal factor occur at different stages of the endocytic pathway. J. Cell. Biol. 166:645–651.

    PubMed  CAS  Google Scholar 

  • Adcock, I.M. (2000). Molecular mechanisms of glucocorticosteroid actions. Pulm. Pharmacol. Ther. 13:115–126.

    PubMed  CAS  Google Scholar 

  • Agrawal, A., Lingappa, J., Leppla, S.H., Agrawal, S., Jabbar, A., Quinn, C., and Pulendran, B. (2003). Impairment of dendritic cells and adaptive immunity by anthrax lethal toxin. Nature 424:329–334.

    PubMed  CAS  Google Scholar 

  • Aranda, A., and Pascual, A. (2001). Nuclear hormone receptors and gene expression. Physiol. Rev. 81:1269–1304.

    PubMed  CAS  Google Scholar 

  • Bergman, N.H., Passalacqua, K.D., Gaspard, R., Shetron-Rama, L.M., Quackenbush, J, and Hanna, P.C. (2005). Murine macrophage transcriptional responses to Bacillus anthracis infection and intoxication. Infect. Immun. 73:1069–1080.

    PubMed  CAS  Google Scholar 

  • Blaustein, R.O., Koehler, T.M., Collier, R.J., and Finkelstein, A. (1989). Anthrax toxin: Channel-forming activity of protective antigen in planar phospholipid bilayers. Proc. Natl. Acad. Sci. U.S.A. 86:2209–2213.

    PubMed  CAS  Google Scholar 

  • Bodwell, J.E., Kingsley, L.A., and Hamilton, J.W. (2004). Arsenic at very low concentrations alters glucocorticoid receptor (GR)-mediated gene activation but not GR-mediated gene repression: Complex dose-response effects are closely correlated with levels of activated GR and require a functional GR DNA binding domain. Chem. Res. Toxicol. 17:1064–1076.

    PubMed  CAS  Google Scholar 

  • Bradley, K.A., Mogridge, J., Mourez, M., Collier, R.J., and Young, J.A. (2001). Identification of the cellular receptor for anthrax toxin. Nature 414:225–229.

    PubMed  CAS  Google Scholar 

  • Bray, P.J., and Cotton, R.G. (2003). Variations of the human glucocorticoid receptor gene (NR3C1): Pathological and in vitro mutations and polymorphisms. Hum. Mutat. 21:557–568.

    PubMed  CAS  Google Scholar 

  • Brogan, I.J., Murray, I.A., Cerillo, G., Needham, M., White, A., and Davis, J.R.E. (1999). Interaction of glucocorticoid receptor isoforms with transcription factors AP-1 and NF-eB: Lack of effect of glucocorticoid receptor Î’. Mol. Cell. Endocrinol. 157:95–104.

    PubMed  CAS  Google Scholar 

  • Buske-Kirschbaum, A., and Hellhammer, D.H. (2003). Endocrine and immune responses to stress in chronic inflammatory skin disorders. Ann. N.Y. Acad. Sci. 992:231–240.

    PubMed  CAS  Google Scholar 

  • Buske-Kirschbaum, A., Jobst, S., Psych, D., Wustman, A., Kirschbaum, C., Rauh, W., and Hellhammer, D. (1997). Attenuated free cortisol response to psychosocial stress in children with atopic dermatitis. Psychosom. Med. 59:419–426.

    PubMed  CAS  Google Scholar 

  • Buske-Kirschbaum, A., Jobst, S., and Hellhammer, D.H. (1998). Altered reactivity of the hypothalamus-pituitary-adrenal axis in patients with atopic dermatitis: Pathologic factor or symptom? Ann. N. Y. Acad. Sci. 840:747–754.

    PubMed  CAS  Google Scholar 

  • Buske-Kirschbaum, A., VonAuer, K., Krieger, S., Weis, S., Rauh, W., and Hellhammer, D. (2003). Blunted cortisol responses to psychosocial stress in asthmatic children: A general feature of atopic disease? Psychosom. Med. 65: 806–810.

    PubMed  CAS  Google Scholar 

  • Calis, M., Gokce, C., Ates, F., Ulker, S., Izgi, H.B., Demir, H., Kirnap, M., Sofuoglu, S., Durak, A.C., Tutus, A., and Kelestimur, E (2004). Investigation of the hypothalamo-pituitary-adrenal axis (HPA) by 1 microg ACTH test and metyrapone test in patients with primary fibromyalgia syndrome. J. Endocrinol. Invest. 27: 42–46.

    PubMed  CAS  Google Scholar 

  • Carlstedt-Duke, J. (1999). Glucocorticoid receptor Î’: View II. Trends Endocrinol. Metab. 10:339–342.

    PubMed  CAS  Google Scholar 

  • Cash, J.M., Crofford, L.J., Gallucci, W.T., Sternberg, E.M., Gold, P.W., Chrousos, G.P., and Wilder, R.L. (1992). Pituitary-adrenal axis responsiveness to ovine corticotropin releasing hormone in patients with rheumatoid arthritis treated with low dose prednisone. J. Rheumatol. 19:1692–1696.

    PubMed  CAS  Google Scholar 

  • Castagliuolo, I., Karalis, K., Valenick, L., Pasha, A., Nikulasson, S., Wlk, M., and Pothoulakis, C. (2001). Endogenous corticosteroids modulate Clostridium difficile toxin A-induced enteritis in rats. Am. J. Physiol. 280:G539–545.

    CAS  Google Scholar 

  • Chandra, H., Gupta, P.K., Sharma, K., Mattoo, A.R., Garg, S.K., Gade, W.N., Sirdeshmukh, R., Maithal, K., and Singh, Y. (2005). Proteome analysis of mouse macrophages treated with anthrax lethal toxin. Biochim. Biophys. Acta 1747: 151–159.

    PubMed  CAS  Google Scholar 

  • Chikanza, I.C. (2002). Mechanisms of corticosteroid resistance in rheumatoid arthritis: A putative role for the corticosteroid receptor beta isoform. Ann. N.Y. Acad. Sci. 966:39–48.

    PubMed  CAS  Google Scholar 

  • Chikanza, I.C., Petrou, P., Kingsley, G., Chrousos, G.P., and Panayi, G.S. (1992): Defective hypothalamic response to immune and inflammatory stimuli in patients with rheumatoid arthritis. Arthritis Rheum. 35:1281–1288.

    PubMed  CAS  Google Scholar 

  • Cole, T.J., Blendy, J.A., Monaghan, A.P., Krieglstein, K., Schmid, W., Aguzzi, A., Fantuzzi, G., Hummler, E., Unsicker, K., and Schutz, G (1995). Targeted disruption of the glucocorticoid receptor gene blocks adrenergic chromaffin cell development and severely retards lung maturation. Genes Dev. 9:1608–1621.

    PubMed  CAS  Google Scholar 

  • Collier, R.J., and Young, J.A. (2003). Anthrax toxin. Annu. Rev. Cell. Dev. Biol. 19: 45–70.

    PubMed  CAS  Google Scholar 

  • Comer, J.E., Galindo, C.L., Chopra, A.K., and Peterson, J.W. (2005). Genechip analyses of global transcriptional responses of murine macrophages to the lethal toxin of Bacillus anthracis. Infect. Immun. 73:1879–1885.

    PubMed  CAS  Google Scholar 

  • Crofford, L.J. (2002). The hypothalamic-pituitary-adrenal axis in the pathogenesis of rheumatic diseases. Endocrinol. Metab. Clin. North Am. 31:1–13.

    PubMed  CAS  Google Scholar 

  • Crofford, L.J., Pillemer, S.R., Kalogeras, K.T., Cash, J.M., Michelson, D., Kling, M.A., Sternberg, E.M., Gold, P.W., Chrousos, G.P., and Wilder, R.L. (1994): Hypothalamic-pituitary-adrenal axis perturbations in patients with fibromyalgia. Arthitis Rheum. 37:1583–1592.

    CAS  Google Scholar 

  • Crofford, L.J., Kalogeras, K.T., Mastorakos, G., Magiakou, M.A., Wells, J., Kanik, K.S., Gold, P.W., Chrousos, G.P., and Wilder, R.L. (1997): Circadian relationships between interleukin (IL)-6 and hypothalamic-pituitary-adrenal axis hormones: Failure of IL-6 to cause sustained hypercortisolism in patients with early untreated rheumatoid arthritis. J. Clin. Endocrinol. Metab. 82:1279–1283.

    PubMed  CAS  Google Scholar 

  • Crofford, L.J., Young, E.A., Engleberg, N.C., Korszun, A., Brucksch, C.B., McClure, L.A., Brown, M.B., and Demitrack, M.A. (2004). Basal circadian and pulsatile ACTH and cortisol secretion in patients with fibromyalgia and/or chronic fatigue syndrome. Brain Behav. Immun. 18:314–325.

    PubMed  CAS  Google Scholar 

  • Cui, X., Moayeri, M., Li, Y., Li, X., Haley, M., Fitz, Y., Correa-Araujo, R., Banks, S.M., Leppla, S.H., and Eichacker, P.Q. (2004). Lethality during continuous anthrax lethal toxin infusion is associated with circulatory shock but not inflammatory cytokine or nitric oxide release in rats. Am. J. Physiol. 286:R699–709.

    CAS  Google Scholar 

  • Cutolo, M., Foppiani, L., Perete, C., Ballarino, P., Sulli, A., Villaggio, B., Seriolo, B., Giusti, M., and Accardo, S. (1999): Hypothalamic-pituitary-adrenocortical axis function in premenopausal women with rheumatoid arthritis not treated with glucocorticoids. J. Rheumatol. 26:282–288.

    PubMed  CAS  Google Scholar 

  • De Bosscher, K., Vanden Berghe, W., and Haegeman, G. (2003). The interplay between the glucocorticoid receptor and nuclear factor-kappaB or activator protein-1: Molecular mechanisms for gene repression. Endocr. Rev. 24:488–522.

    PubMed  Google Scholar 

  • Demitrack, M.A., and Crofford, L.J. (1998). Evidence for and pathophysiologic implications of hypothalamic-pituitary-adrenal axis dysregulation in fibromyalgia and chronic fatigue syndrome. Ann. N. Y. Acad. Sci. 840:684–697.

    PubMed  CAS  Google Scholar 

  • Demitrack, M.A., Dale, J.K., Straus, S.E., Laue, L., Listwak, S.J., Kruesi, M.J., Chrousos, G.P., and Gold, P.W. (1991): Evidence for impaired activation of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome. J. Clin. Endocrinol. Metab. 73:1224–1234.

    PubMed  CAS  Google Scholar 

  • DeRijk, R.H., Schaaf, M.J., Turner, G., Datson, N.A., Vreugdenhil, E., Cidlowski, J., de Kloet, E.R., Emery, P., Sternberg, E.M., and Detera-Wadleigh, S.D. (2001). A human glucocorticoid receptor gene variant that increases the stability of the glucocorticoid receptor beta-isoform mRNA is associated with rheumatoid arthritis. J. Rheumatol. 28:2383–2388.

    PubMed  CAS  Google Scholar 

  • Diaz-Borjon, A., Richaud-Patin, Y., Alvarado de la Barrera, C., Jakez-Ocampo, J., Ruiz-Arguelles, A., and Llorente, L. (2000). Multidrug resistance-1 (MDR-1) in rheumatic autoimmune disorders. Part II: Increased P-glycoprotein activity in lymphocytes from systemic lupus erythematosus patients might affect steroid requirements for disease control. Joint Bone Spine 67:40–48.

    PubMed  CAS  Google Scholar 

  • Dorner, C., Ciossek, T., Muller, S., Moller, P.H., Ullrich, A., and Lammers, R. (1998): Characterization of Kif1c, a new kinesin-like protein involved in vesicle transport from the golgi apparatus to the endoplasmic reticulum. J. Biol. Chem. 273: 20267–20275.

    PubMed  CAS  Google Scholar 

  • Drouin, J., Sun, Y.L., and Nemer, M. (1989). Glucocorticoid repression of pro-opiomelanocortin gene transcription. J. Steroid Biochem. 34:63–69.

    PubMed  CAS  Google Scholar 

  • Duesbery, N.S., Webb, C.P., Leppla, S.H., Gordon, V.M., Klimpel, K.R., Copeland, T.D., Ahn, N.G., Oskarsson, M.K., Fukasawa, K., Paull, K.D., and VandeWoude, G.F. (1998). Proteolytic inactivation of map-kinase-kinase by anthrax lethal factor. Science 280:734–737.

    PubMed  CAS  Google Scholar 

  • Edwards, C.K.I., Yunger, L.M., Lorence, R.M., Dantzer, R., and Kelley, K.W. (1991). The pituitary gland is required for protection against lethal effects of Salmonella typhimurium. Proc. Natl. Acad. Sci. U.S.A. 88:2274–2277.

    PubMed  CAS  Google Scholar 

  • Eijsbouts, A.M., and Murphy, E.P. (1999). The role of the hypothalamic-pituitary-adrenal axis in rheumatoid arthritis. Baillieres Best Pract. Res. Clin. Rheumatol. 13:599–613.

    PubMed  CAS  Google Scholar 

  • Erwin, J.L., DaSilva, L.M., Bavari, S., Little, S.F., Friedlander, A.M., and Chanh, T.C. (2001). Macrophage-derived cell lines do not express proinflammatory cytokines after exposure to Bacillus anthracis lethal toxin. Infect. Immun. 69:1175–1177.

    PubMed  CAS  Google Scholar 

  • Evans, R.M. (1988). The steroid and thyroid hormone receptor superfamily. Science 240:889–895.

    PubMed  CAS  Google Scholar 

  • Ezzell, J.W., Ivins, B.E., and Leppla, S.H. (1984). Immunoelectrophoretic analysis, toxicity, and kinetics of in vitro production of the protective antigen and lethal factor components of Bacillus anthracis toxin. Infect. Immun. 45:761–767.

    PubMed  CAS  Google Scholar 

  • Fakhri, S., Christodoulopoulos, P., Tulic, M., Fukakusa, M., Frenkiel, S., Leung, D.Y., and Hamid, Q. A. (2003). Role of microbial toxins in the induction of glucocorticoid receptor beta expression in an explant model of rhinosinusitis. J. Otolaryngol. 32:388–393.

    PubMed  Google Scholar 

  • Fakhri, S., Tulic, M., Christodoulopoulos, P., Fukakusa, M., Frenkiel, S., Leung, D.Y., and Hamid, Q.A. (2004). Microbial superantigens induce glucocorticoid receptor beta and steroid resistance in a nasal explant model. Laryngoscope 114:887–892.

    PubMed  Google Scholar 

  • Farrell, R.J., Murphy, A., Long, A., Donnelly, S., Cherikuri, A., O’Toole, D., Mahmud, N., Keeling, P.W., Weir, D.G., and Kelleher, D. (2000). High multidrug resistance (P-glycoprotein 170) expression in inflammatory bowel disease patients who fail medical therapy. Gastroenterology 118:279–288.

    PubMed  CAS  Google Scholar 

  • Fish, D.C., Klein, F., Lincoln, R.E., Walker, J.S., and Dobbs, J.P. (1968). Pathophysiological changes in the rat associated with anthrax toxin. J. Infect. Dis. 118: 114–124.

    PubMed  CAS  Google Scholar 

  • Friedlander, A.M. (1986). Macrophages are sensitive to anthrax lethal toxin through an acid-dependent process. J. Biol. Chem. 261:7123–7126.

    PubMed  CAS  Google Scholar 

  • Friedlander, A.M., Bhatnagar, R., Leppla, S.H., Johnson, L., and Singh, Y. (1993). Characterization of macrophage sensitivity and resistance to anthrax lethal toxin. Infect. Immun. 61:245–252.

    PubMed  CAS  Google Scholar 

  • Gaab, J., Huster, D., Peisen, R., Engert, V., Heitz, V., Schad, T., Schurmeyer, T.H., and Ehlert, U. (2002). Hypothalamic-pituitary-adrenal axis reactivity in chronic fatigue syndrome and health under psychological, physiological, and pharmacological stimulation. Psychosom. Med. 64:951–962.

    PubMed  CAS  Google Scholar 

  • Gaab, J., Engert, V., Heitz, V., Schad, T., Schurmeyer, T.H., and Ehlert, U. (2004). Associations between neuroendocrine responses to the insulin tolerance test and patient characteristics in chronic fatigue syndrome. J. Psychosom. Res. 56:419–424.

    PubMed  Google Scholar 

  • Gutierrez, M.A., Garcia, M.E., Rodriguez, J.A., Rivero, S., and Jacobelli, S. (1998). Hypothalamic-pituitary-adrenal axis function and prolactin secretion in systemic lupus erythematosus. Lupus 7:404–408.

    PubMed  CAS  Google Scholar 

  • Gutierrez, M.A., Garcia, M.E., Rodriguez, J.A., Mardonez, G., Jacobelli, S., and Rivero, S. (1999). Hypothalamic-pituitary-adrenal axis function in patients with active rheumatoid arthritis: A controlled study using insulin hypoglycemia stress test and prolactin stimulation. J. Rheumatol. 26:277–281.

    PubMed  CAS  Google Scholar 

  • Gómez, F., deKloet, E.R., and Armario, A. (1998). Glucocorticoid negative feedback on the HPA axis in five inbred rat strains. Am. J. Physiol. 274:R420–R427.

    PubMed  Google Scholar 

  • Haarman, E.G., Kaspers, G.J., Pieters, R., Rottier, M.M., and Veerman, A.J. (2004). Glucocorticoid receptor alpha, beta and gamma expression vs. in vitro glucocorticoid resistance in childhood leukemia. Leukemia 18:530–537.

    PubMed  CAS  Google Scholar 

  • Hamid, Q.A., Wenzel, S.E., Hauk, P.J., Tsicopoulos, A., Wallaert, B., Lafitte, J.-J., Chrousos, G.P., Szefler, S.J., and Leung, D.Y.M. (1999). Increased glucocorticoid receptor Î’ in airway cells of glucocorticoid-insensitive asthma. Am. J. Respir. Crit. Care Med. 159:1600–1604.

    PubMed  CAS  Google Scholar 

  • Hamilos, D.L., Leung, D.Y., Muro, S., Kahn, A.M., Hamilos, S.S., Thawley, S.E., and Hamid, Q.A. (2001). GRbeta expression in nasal polyp inflammatory cells and its relationship to the anti-inflammatory effects of intranasal fluticasone. J. Allergy Clin. Immunol. 108:59–68.

    PubMed  CAS  Google Scholar 

  • Hammond, S.E., and Hanna, P.C. (1998). Lethal factor active-site mutations affect catalytic activity in vitro. Infect. Immun. 66:2374–2378.

    PubMed  CAS  Google Scholar 

  • Hamrahian, A.H., Oseni, T.S., and Arafah, B.M. (2004). Measurements of serum free cortisol in critically ill patients. N. Engl. J. Med. 350:1629–1638.

    PubMed  CAS  Google Scholar 

  • Hanna, P.C., Acosta, D., and Collier, R.J. (1993). On the role of macrophages in anthrax. Proc. Natl. Acad. Sci. U.S.A. 90:10198–10201.

    PubMed  CAS  Google Scholar 

  • Hecht, K., Carlstedt-Duke, J., Stierna, P., Gustafsson, J.-Ã¥., BrönnegÃ¥rd, M., and Wikström, A.-C (1997). Evidence that the Î’-isoform of the human glucocorticoid receptor does not act as a physiologically significant repressor. J. Biol. Chem. 272: 26659–26664.

    PubMed  CAS  Google Scholar 

  • Herrlich, E(2001). Cross-talk between glucocorticoid receptor and AP-1. Oncogene 20:2465–2475.

    Google Scholar 

  • Hirano, T., Onda, K., Toma, T., Miyaoka, M., Moriyasu, F., and Oka, K. (2004). MDR1 mRNA expressions in peripheral blood mononuclear cells of patients with ulcerative colitis in relation to glucocorticoid administration. J. Clin. Pharmacol. 44: 481–486.

    Google Scholar 

  • Honda, M., Orii, F., Ayabe, T., Imai, S., Ashida, T., Obara, T., and Kohgo, Y. (2000). Expression of glucocorticoid receptor Î’ in lymphocytes of patients with glucocorticoid-resistant ulcerative colitis. Gastroenterology 118:859–866.

    PubMed  CAS  Google Scholar 

  • Hori, T., Watanabe, K., Miyaoka, M., Moriyasu, F., Onda, K., Hirano, T., and Oka, K. (2002). Expression of mRNA for glucocorticoid receptors in peripheral blood mononuclear cells of patients with Crohn’s disease. J. Gastroenterol. Hepatol. 17: 1070–1077.

    PubMed  CAS  Google Scholar 

  • Hu, Y., Dietrich, H., Herold, M., Heinrich, P.C., and Wick, G. (1993). Disturbed immuno-endocrine communication via the hypothalamo-pituitary-adrenal axis in autoimmune disease. Int. Arch. Allergy Immunol. 102:232–241.

    PubMed  CAS  Google Scholar 

  • Huitinga, I., Erkut, Z.A., vanBeurden, D., and Swaab, D.F. (2003). The hypothalamo-pituitary-adrenal axis in multiple sclerosis. Ann. N. Y.Acad. Sci. 992:118–128.

    PubMed  CAS  Google Scholar 

  • Huizenga, N.A.T.M., Koper, J.W., DeLange, P., Pols, H.A.P., Stolk, R.P., Burger, H., Grobbee, D.E., Brinkmann, A.O., De Jong, F.H., and Lamberts, S.W.J. (1998). A polymorphism in the glucocorticoid receptor gene may be associated with an increased sensitivity to glucocorticoids in vivo. J. Clin. Endocrinol. Metab. 83: 144–151.

    PubMed  CAS  Google Scholar 

  • Irusen, E., Matthews, J.G., Takahashi, A., Barnes, P.J., Chung, K.F., and Adcock, I.M. (2002). p38 mitogen-activated protein kinase-induced glucocorticoid receptor phosphorylation reduces its activity: Role in steroid-insensitive asthma. J. Allergy Clin. Immunol. 109:649–657.

    PubMed  CAS  Google Scholar 

  • Jantzen, H.M., Strahle, U., Gloss, B., Stewart, F., Schmid, W., Boshart, M., Miksicek, R., and Schutz, G. (1987). Cooperativity of glucocorticoid response elements located far upstream of the tyrosine aminotransferase gene. Cell 49:29–38.

    PubMed  CAS  Google Scholar 

  • Johnson, E.O., Vlachoyiannopoulos, P.G., Skopouli, F.N., Tzioufas, A.G., and Moutsopoulos, H.M. (1998). Hypofunction of the stress axis in Sjogren’s syndrome. J. Rheumatol. 25:1508–1514.

    PubMed  CAS  Google Scholar 

  • Kalns, J., Scruggs, J., Millenbaugh, N., Vivekananda, J., Shealy, D., Eggers, J., and Kiel, J. (2002). TNF receptor 1, IL-1 receptor, and iNOS genetic knockout mice are not protected from anthrax infection. Biochem. Biophys. Res. Commun. 292:41–44.

    PubMed  CAS  Google Scholar 

  • Karin, M., and Chang, L. (2001). AP-1-glucocorticoid receptor crosstalk taken to a higher level. J. Endocrinol. 169:447–451.

    PubMed  CAS  Google Scholar 

  • Kassam, A., Der, S.D., and Mogridge, J. (2005). Differentiation of human monocytic cell lines confers susceptibility to Bacillus anthracis lethal toxin. Cell. Microbiol. 7:281–292.

    PubMed  CAS  Google Scholar 

  • Kim, S.O., Jing, Q., Hoebe, K., Beutler, B., Duesbery, N.S., and Han, J. (2003). Sensitizing anthrax lethal toxin-resistant macrophages to lethal toxin-induced killing by tumor necrosis factor-alpha. J. Biol. Chem. 278:7413–7421.

    PubMed  CAS  Google Scholar 

  • Kino, T., and Chrousos, G.P. (2001). Glucocorticoid and mineralocorticoid resistance/hypersensitivity syndromes. J. Endocrinol. 169:437–445.

    PubMed  CAS  Google Scholar 

  • Kino, T., Gragerov, A., Kopp. J.B., Stauber, R.H., Pavlakis, G.N., and Chrousos, G.P. (1999). The HIV-1 virion-associated protein Vpr is a coactivator of the human glucocorticoid receptor. J. Exp. Med. 189:51–61.

    PubMed  CAS  Google Scholar 

  • Kirby, J.E. (2004). Anthrax lethal toxin induces human endothelial cell apoptosis. Infect. Immun. 72:430–439.

    PubMed  CAS  Google Scholar 

  • Klein, F., Hodges, D.R., Mahlandt, B.G., Jones, W.I., Haines, B.W., and Lincoln, R.E. (1962). Anthrax toxin: Causative agent in the death of rhesus monkeys. Science 138:1331–1333.

    PubMed  CAS  Google Scholar 

  • Klimpel, K.R., Molloy, S.S., Thomas, G., and Leppla, S.H. (1992). Anthrax toxin protective antigen is activated by a cell surface protease with the sequence specificity and catalytic properties of furin. Proc. Natl. Acad. Sci. U.S.A. 89:10277–10281.

    PubMed  CAS  Google Scholar 

  • Klimpel, K.R., Arora, N., and Leppla, S.H. (1994). Anthrax toxin lethal factor contains a zinc metalloprotease consensus sequence which is required for lethal toxin activity. Mol. Microbiol. 13:1093–1100.

    PubMed  CAS  Google Scholar 

  • Knutti, D., Kressler, D., and Kralli, A. (2001). Regulation of the transcriptional coactivator PGC-1 via MAPK-sensitive interaction with a repressor. Proc. Natl. Acad. Sci. U.S.A. 98:9713–9718.

    PubMed  CAS  Google Scholar 

  • Koper, J.W., Stolk, R.P., De Lange, P., Huizenga, N.A.T.M., Molijn, G.-J., Pols, H.A.P., Grobbee, D.E., Karl, M., De Jong, F.H., Brinkmann, A.O., and Lamberts, S.W.J. (1997). Lack of association between five polymorphisms in the human glucocorticoid receptor gene and glucocorticoid resistance. Hum. Genet. 99:663–668.

    PubMed  CAS  Google Scholar 

  • Kozawa, O., Niwa, M., Hatakeyama, D., Tokuda, H., Oiso, Y., Matsuno, H., Kato, K., and Uematsu, T. (2002). Specific induction of heat shock protein 27 by glucocorticoid in osteoblasts. J. Cell. Biochem. 86:357–364.

    PubMed  CAS  Google Scholar 

  • Kralli, A.R., and Yamamoto. K.R. (1996). An FK506-sensitive transporter selectively decreases intracellular levels and potency of steroid hormones. J. Biol. Chem. 271: 17152–17156.

    PubMed  CAS  Google Scholar 

  • Krstic, M.D., Rogatsky, I., Yamamoto, K.R., and Garabedian, M.J. (1997). Mitogen-activated and cyclin-dependent protein kinases selectively and differentially modulate transcriptional enhancement by the glucocorticoid receptor. Mol. Cell. Biol. 17:3947–3954.

    PubMed  CAS  Google Scholar 

  • Lechner, O., Hu, Y., Jafarian Tehrani, M., Dietrich, H., Schwartz, S., Herold, M., Haour, F., and Wick, G. (1996). Disturbed immunoendocine communication via the hypothalamo-pituitary-adrenal axis in murine lupus. Brain Behav. Immun. 10: 337–350.

    PubMed  CAS  Google Scholar 

  • Leung, D.Y.M., Hamid, Q., Vottero, A., Szefler, S.J., Surs, W., Minshall, E., Chrousos, G.P., and Klemm, D.J. (1997). Association of glucocorticoid insensitivity with increased expression of glucocorticoid receptor Î’. J. Exp. Med. 186:1567–1574.

    PubMed  CAS  Google Scholar 

  • Lindsay, R.S., Wake, D.J., Nair, S., Bunt, J., Livingstone, D.E., Permana, P.A., Tataranni, P.A., and Walker, B.R. (2003). Subcutaneous adipose 11 beta-hydroxysteroid dehydrogenase type 1 activity and messenger ribonucleic acid levels are associated with adiposity and insulinemia in Pima Indians and Caucasians. J. Clin. Endocrinol. Metab. 88:2738–2744.

    PubMed  CAS  Google Scholar 

  • Llorente, L., Richaud-Patin, Y., Diaz-Borjon, A., Alvaradode la Barrera, C, Jakez-Ocampo, J., de la Fuente, H., Gonzalez-Amaro, R., and Diaz-Jouanen, E. (2000). Multidrug resistance-1 (MDR-1) in rheumatic autoimmune disorders. Part I: Increased P-glycoprotein activity in lymphocytes from rheumatoid arthritis patients might influence disease outcome. Joint Bone Spine 67:30–39.

    PubMed  CAS  Google Scholar 

  • Lopez, G.N., Turck, C.W., Schaufele, F., Stallcup, M.R., and Kushner, P.J. (2001). Growth factors signal to steroid receptors through mitogen-activated protein kinase regulation of p160 coactivator activity. J. Biol. Chem. 276:22177–22182.

    PubMed  CAS  Google Scholar 

  • Lucibello, F.C., Slater, E.P., Jooss, K.U., Beato, M., and Muller, R. (1990). Mutual transrepression of Fos and the glucocorticoid receptor: Involvement of a functional domain in Fos which is absent in FosB. EM BO J. 9:2827–2834.

    CAS  Google Scholar 

  • MacPhee, I.A.M., Antoni, F.A., and Mason, D.W. (1989). Spontaneous recovery of rats from experimental allergic encephalomyelitis is dependent on regulation of the immune system by endogenous adrenal corticosteroids. J. Exp. Med. 169: 431–445.

    PubMed  CAS  Google Scholar 

  • McAllister, R.D., Singh, Y., Du Bois, W.D., Potter, M., Boehm, T., Meeker, N.D., Fillmore, P.D., Anderson, L.M., Poynter, M.E., and Teuscher, C. (2003). Susceptibility to anthrax lethal toxin is controlled by three linked quantitative trait loci. Am. J. Pathol. 163:1735–1741.

    PubMed  CAS  Google Scholar 

  • McCallum, R.E., and Stith, R.D. (1982). Endotoxin-induced inhibition of steroid binding by mouse liver cytosol. Circ. Shock 9:357–367.

    PubMed  CAS  Google Scholar 

  • McKay, L.I., and Cidlowski, J.A. (1999). Molecular control of immune/inflammatory responses: Interactions between nuclear factor-kappa B and steroid receptor-signaling pathways. Endocr. Rev. 20:435–459.

    PubMed  CAS  Google Scholar 

  • Medh, R.D., Lay, R.H., and Schmidt, T.J. (1998). Agonist-specific modulation of glucocorticoid receptor-mediated transcription by immunosuppressants. Mol. Cell. Endocrinol. 138:11–23.

    PubMed  CAS  Google Scholar 

  • Menard, A., Papini, E., Mock, M., and Montecucco, C. (1996). The cytotoxic activity of Bacillus anthracis lethal factor is inhibited by leukotriene A4 hydrolase and metallopeptidase inhibitors. Biochem. J. 320:687–691.

    PubMed  CAS  Google Scholar 

  • Michelson, D., Stone, L., Galliven, E., Magiakou, M.A., Chrousos, G.P., Sternberg, E.M., and Gold, P.W. (1994). Multiple sclerosis is associated with alterations in hypothalamic-pituitary-adrenal axis function. J. Clin. Endocrinol. Metab. 79:848–853.

    PubMed  CAS  Google Scholar 

  • Mingrone, G., DeGaetano, A., Pugeat, M., Capristo, E., Greco, A.V., and Gasbarrini, G (1999). The steroid resistance of Crohn’s disease. J. Invest. Med. 47:319–325.

    CAS  Google Scholar 

  • Moayeri, M., Haines, D., Young, H.A., and Leppla, S.H. (2003): Bacillus anthracis lethal toxin induces TNF-alpha-independent hypoxia-mediated toxicity in mice. J. Clin. Invest. 112:670–682.

    PubMed  CAS  Google Scholar 

  • Moayeri, M., Martinez, N.W., Wiggins, J., Young, H.A., and Leppla, S.H. (2004). Mouse susceptibility to anthrax lethal toxin is influenced by genetic factors in addition to those controlling macrophage sensitivity. Infect. Immun. 72:4439–4447.

    PubMed  CAS  Google Scholar 

  • Moayeri, M., Webster, J.I., Wiggins, J.F., Leppla, S.H., and Sternberg, E.M. (2005). Endocrine perturbation increases susceptibility of mice to anthrax lethal toxin. Infect. Immun. 73:4238–4244.

    PubMed  CAS  Google Scholar 

  • Mock, M., and Fouet, A. (2001). Anthrax. Annu. Rev. Microbiol. 55:647–671.

    PubMed  CAS  Google Scholar 

  • Moncek, F., Kvetnansky, R., and Jezova, D. (2001). Differential responses to stress stimuli of Lewis and Fischer rats at the pituitary and adrenocortical level. Endocr. Reg. 35:35–41.

    CAS  Google Scholar 

  • Mykoniatis, A., Anton, P.M., Wlk, M., Wang, C.C., Ungsunan, L., Bluher, S., Venihaki, M., Simeonidis, S., Zacks, J., Zhao, D., Sougioultzis, S., Karalis, K., Mantzoros, C., and Pothoulakis, C. (2003). Leptin mediates Clostridium difficile toxin A-induced enteritis in mice. Gastroenterology 124:683–691.

    PubMed  CAS  Google Scholar 

  • Neeck, G., and Crofford, L.J. (2000). Neuroendocrine perturbations in fibromyalgia and chronic fatigue syndrome. Rheum. Dis. Clin. North Am. 26:989–1002.

    PubMed  CAS  Google Scholar 

  • New, M.I., Nimkarn, S., Brandon, D.D., Cunningham-Rundles, S., Wilson, R.C., Newfield, R.S., Vandermeulen, J., Barron, N., Russo, C., Loriaux, D.L., and O’Malley, B. (1999). Resistance to several steroids in two sisters. J. Clin. Endocrinol. Metab. 84:4454–4464.

    PubMed  CAS  Google Scholar 

  • New, M.I., Nimkarn, S., Brandon, D.D., Cunningham-Rundles, S., Wilson, R.C., Newfield, R.S., Vandermeulen, J., Barron, N., Russo, C., Loriaux, D.L., and O’Malley, B. (2001). Resistance to multiple steroids in two sisters. J. Steroid Biochem. Mol. Biol. 76:161–166.

    PubMed  CAS  Google Scholar 

  • Oakley, R.H., Sar, M., and Cidlowski, J.A. (1996). The human glucocorticoid receptor b isoform. Expression, biochemical properties and putative function. J. Biol. Chem. 271:9550–9559.

    PubMed  CAS  Google Scholar 

  • Oakley, R.H., Jewell, C.M., Yudt, M.R., Bofetiado, D.M., and Cidlowski, J.A. (1999). The dominant negative activity of the human glucocorticoid receptor Î’ isoform. Specificity and mechanisms of action. J. Biol. Chem. 274:27857–27866.

    PubMed  CAS  Google Scholar 

  • Orii, F., Ashida, T., Nomura, M., Maemoto, A., Fujiki, T., Ayabe, T., Imai, S., Saitoh, Y., and Kohgo, Y. (2002). Quantitative analysis for human glucocorticoid receptor alpha/beta mRNA in IBD. Biochem. Biophys. Res. Commun. 296:1286–1294.

    PubMed  CAS  Google Scholar 

  • Paccani, S.R., Tonello, F., Ghittoni, R., Natale, M., Muraro, L., D’Elios, M.M., Tang, W.J., Montecucco, C., and Baldari, C.T (2005). Anthrax toxins suppress T lymphocyte activation by disrupting antigen receptor signaling. J. Exp. Med. 201: 325–331.

    PubMed  CAS  Google Scholar 

  • Palermo, M., Alves-Rosa, F., Rubel, C., Fernandez, G.C., Fernandez-Alonso, G., Alberto, F., Rivas, M., and Isturiz, M. (2000). Pretreatment of mice with lipopolysaccharide (LPS) or IL-1beta exerts dose-dependent opposite effects on Shiga toxin-2 lethality. Clin. Exp. Immunol. 119:77–83.

    PubMed  CAS  Google Scholar 

  • Pandey, J., and Warburton, D. (2004). Knock-on effect of anthrax lethal toxin on macrophages potentiates cytotoxicity to endothelial cells. Microbes Infect. 6: 835–843.

    PubMed  CAS  Google Scholar 

  • Park, J.M., Greten, F.R., Li, Z.W., and Karin, M. (2002). Macrophage apoptosis by anthrax lethal factor through p38 map kinase inhibition. Science 297:2048–2051.

    PubMed  CAS  Google Scholar 

  • Pellizzari, R., Guidi-Rontani, C., Vitale, G., Mock, M., and Montecucco, C. (1999). Anthrax lethal factor cleaves MKK3 in macrophages and inhibits the LPS/IFNγ-induced release of NO and TNFα. FEBS Lett. 462:199–204.

    PubMed  CAS  Google Scholar 

  • Pellizzari, R., Guidi-Rontani, C., Vitale, G., Mock, M., and Montecucco, C. (2000). Lethal factor of Bacillus anthracis cleaves the N-terminus of MAPKKs: Analysis of the intracellular consequences in macrophages. Int. J. Med. Microbiol. 290: 421–427.

    PubMed  CAS  Google Scholar 

  • Pezard, C., Berche, P., and Mock, M. (1991). Contribution of individual toxin components to virulence of Bacillus anthracis. Infect. Immun. 59:3472–3477.

    PubMed  CAS  Google Scholar 

  • Pickering, A.K., and Merkel, T.J. (2004). Macrophages release tumor necrosis factor alpha and interleukin-12 in response to intracellular Bacillus anthracis spores. Infect. Immun. 72:3069–3072.

    PubMed  CAS  Google Scholar 

  • Pickering, A.K., Osorio, M., Lee, G.M., Grippe, V.K., Bray, M., and Merkel, T.J. (2004). Cytokine response to infection with Bacillus anthracis spores. Infect. Immun. 72:6382–6389.

    PubMed  CAS  Google Scholar 

  • Popov, S.G., Villasmil, R., Bernardi, J., Grene, E., Cardwell, J., Popova, T., Wu, A., Alibek, D., Bailey, C., and Alibek, K. (2002a). Effect of Bacillus anthracis lethal toxin on human peripheral blood mononuclear cells. FEBS Lett. 527:211–215.

    PubMed  CAS  Google Scholar 

  • Popov, S.G., Villasmil, R., Bernardi, J., Grene, E., Cardwell, J., Wu, A., Alibek, D., Bailey, C., and Alibek, K. (2002b). Lethal toxin of Bacillus anthracis causes apoptosis of macrophages. Biochem. Biophys. Res. Commun. 293:349–355.

    PubMed  CAS  Google Scholar 

  • Popov, S.G., Popova, T.G., Grene, E., Klotz, F., Cardwell, J., Bradburne, C., Jama, Y., Maland, M., Wells, J., Nalca, A., Voss, T., Bailey, C., and Alibek, K. (2004). Systemic cytokine response in murine anthrax. Cell. Microbiol. 6:225–233.

    PubMed  CAS  Google Scholar 

  • Pujols, L., Mullol, J., Benitez, P., Torrego, A., Xaubet, A., de Haro, J., and Picado, C. (2003). Expression of the glucocorticoid receptor alpha and beta isoforms in human nasal mucosa and polyp epithelial cells. Respir. Med. 97:90–96.

    PubMed  Google Scholar 

  • Pujols, L., Xaubet, A., Ramirez, J., Mullol, J., Roca-Ferrer, J., Torrego, A., Cidlowski, J.A., and Picado, C. (2004). Expression of glucocorticoid receptors alpha and beta in steroid sensitive and steroid insensitive interstitial lung diseases. Thorax 59: 687–693.

    PubMed  CAS  Google Scholar 

  • Racciatti, D., Guagnano, M.T., Vecchiet, J., De Remigis, P.L., Pizzigallo, E., Della Vecchia, R., Di Sciascio, T., Merlitti, D., and Sensi, S. (2001). Chronic fatigue syndrome: Circadian rhythm and hypothalamic-pituitary-adrenal (HPA) axis impairment. Int. J. Immunopathol. Pharmacol. 14:11–15.

    PubMed  CAS  Google Scholar 

  • Rask, E., Olsson, T., Soderberg, S., Andrew, R., Livingstone, D.E., Johnson, O., and Walker, B.R. (2001). Tissue-specific dysregulation of cortisol metabolism in human obesity. J. Clin. Endocrinol. Metab. 86:1418–1421.

    PubMed  CAS  Google Scholar 

  • Reichardt, H.M., Kaestner, K.H., Tuckermann, J., Kretz, O., Wessely, O., Bock, R., Gass, P., Schmid, W., Herrlich, P., Angel, P., and Schütz, G. (1998). DNA binding of the glucocorticoid receptor is not essential for survival. Cell 93:531–541.

    PubMed  CAS  Google Scholar 

  • Richaud-Patin, Y., Vega-Boada, F., Vidaller, A., and Llorente, L. (2004). Multidrug resistance-1 (MDR-1) in autoimmune disorders IV. P-glycoprotein overfunction in lymphocytes from myasthenia gravis patients. Biomed. Pharmacother. 58:320–324.

    PubMed  CAS  Google Scholar 

  • Roberts, J.E., Watters, J.W., Ballard, J.D., and Dietrich, W.F. (1998). Ltx1, a mouse locus that influences the susceptibility of macrophages to cytolysis caused by intoxication with Bacillus anthracis lethal factor, maps to chromosome 11. Mol. Microbiol. 29:581–591.

    PubMed  CAS  Google Scholar 

  • Roberts, A.D., Wessely, S., Chalder, T., Papadopoulos, A., and Cleare, A.J. (2004). Salivary cortisol response to awakening in chronic fatigue syndrome. Br. J. Psychiatry 184:136–141.

    PubMed  Google Scholar 

  • Rogatsky, I., Logan, S.K., and Garabedian, M.J. (1998). Antagonism of glucocorticoid receptor transcriptional activation by the c-Jun N-terminal kinase. Proc. Natl. Acad. Sci. U.S.A. 95:2050–2055.

    PubMed  CAS  Google Scholar 

  • Rupprecht, M., Hornstein, O.P., Schluter, D., Schafers, H.J., Koch, H.U., Beck, G., and Rupprecht, R. (1995). Cortisol, corticotropin, and beta-endorphin responses to corticotropin-releasing hormone in patients with atopic eczema. Psychoneuroendocrinology 20:543–551.

    PubMed  CAS  Google Scholar 

  • Ruzek, M.C., Pearce, B.D., Miller, A.H., and Biron, C.A. (1999). Endogenous glucocorticoids protect against cytokine-mediated lethality during viral infection. J. Immunol. 162:3527–3533.

    PubMed  CAS  Google Scholar 

  • Schlaghecke, R., Kornely, E., Wollenhaupt, J., and Specker, C. (1992). Glucocorticoid receptors in rheumatoid arthritis. Arthritis Rheum. 35:740–744.

    PubMed  CAS  Google Scholar 

  • Schoneveld, O.J., Gaemers, I.C., and Lamers, W.H. (2004). Mechanisms of glucocorticoid signalling. Biochim. Biophys. Acta 1680:114–128.

    PubMed  CAS  Google Scholar 

  • Schule, R., Rangarajan, P., Kliewer, S., Ransone, L.J., Bolado, J., Yang, N., Verma, I.M., and Evans, R.M. (1990). Functional antagonism between oncoprotein c-Jun and the glucocorticoid receptor. Cell 62:1217–1226.

    PubMed  CAS  Google Scholar 

  • Scobie, H.M., Rainey, G.J., Bradley, K.A., and Young, J.A. (2003). Human capillary morphogenesis protein 2 functions as an anthrax toxin receptor. Proc. Natl. Acad. Sci. U.S.A. 100:5170–5174.

    PubMed  CAS  Google Scholar 

  • Seckl, J.R., and Walker, B.R. (2001). Minireview: 11Î’-hydroxysteroid dehydrogenase type 1—A tissue-specific amplifier of glucocorticoid action. Endocrinology 142: 1371–1376.

    PubMed  CAS  Google Scholar 

  • Seckl, J.R., Morton, N.M., Chapman, K.E., and Walker, B.R. (2004). Glucocorticoids and 11beta-hydroxysteroid dehydrogenase in adipose tissue. Recent Prog. Horm. Res. 59:359–393.

    PubMed  CAS  Google Scholar 

  • Shahidi, H., Vottero, A., Stratakis, C., Taymans, S.E., Karl, M., Longui, C.A., Chrousos, G.P., Daughaday, W.H., Gregory, S.A., and Plate, J.M.D. (1999). Imbalanced expression of the glucocorticoid receptor isoforms in cultured lymphocytes from a patient with systemic glucocorticoid resistance and chronic lymphocytic leukemia. Biochem. Biophys. Res. Commun. 254:559–565.

    PubMed  CAS  Google Scholar 

  • Shanks, N., Griffiths, J., Zalcman, S., Zacharko, R.M., and Anisman, H. (1990). Mouse strain differences in plasma corticosterone following uncontrollable footshock. Pharmacol. Biochem. Behav. 36:515–519.

    PubMed  CAS  Google Scholar 

  • Shin, S., Hur, G.H., Kim, Y.B., Yeon, G.B., Park, K.J., Park, Y.M., and Lee, W.S. (2000). Dehydroepiandrosterone and melatonin prevent Bacillus anthracis lethal toxininduced TNF production in macrophages. Cell. Biol. Toxicol. 16:165–174.

    PubMed  CAS  Google Scholar 

  • Singh, Y., Leppla, S.H., Bhatnagar, R., and Friedlander, A.M. (1989). Internalization and processing of Bacillus anthracis lethal toxin by toxin-sensitive and-resistant cells. J. Biol. Chem. 264:11099–11102.

    PubMed  CAS  Google Scholar 

  • Singh, Y., Klimpel, K.R., Goel, S., Swain, P.K., and Leppla, S.H. (1999). Oligomerization of anthrax toxin protective antigen and binding of lethal factor during endocytic uptake into mammalian cells. Infect. Immun. 67:1853–1859.

    PubMed  CAS  Google Scholar 

  • Smith, H., Keppie. J., Stanley, J.L., and Harris-Smith, P.W (1955). The chemical basis of the virulence of Bacillus anthracis. IV: Secondary shock as the major factor in death of guinea-pigs from anthrax. Br. J. Exp. Pathol. 36:323–335.

    PubMed  CAS  Google Scholar 

  • Smoak, K.A., and Cidlowski, J. A. (2004). Mechanisms of glucocorticoid receptor signaling during inflammation. Mech. Ageing Dev. 125:697–706.

    PubMed  CAS  Google Scholar 

  • Sousa, A.R., Lane, S.J., Cidlowski, J.A., Staynov, D.Z., and Lee, T.H. (2000). Glucocorticoid resistance in asthma is associated with elevated in vivo expression of the glucocorticoid receptor beta-isoform. J. Allergy Clin. Immunol. 105:943–950.

    PubMed  CAS  Google Scholar 

  • Sternberg, E.M., Hill, J.M., Chrousos, G.P., Kamilaris, T., Listwak, S.J., Gold, P.W., and Wilder, R.L. (1989a). Inflammatory mediator-induced hypothalamic-pituitary-adrenal axis activation is defective in streptococcal cell wall arthritis-susceptible Lewis rats. Proc. Natl. Acad. Sci. U.S.A. 86:2374–2378.

    PubMed  CAS  Google Scholar 

  • Sternberg, E.M., Young, W.S.d., Bernardini, R., Calogero, A.E., Chrousos, G.P., Gold, P.W., and Wilder, R.L. (1989b). A central nervous system defect in biosynthesis of corticotropin-releasing hormone is associated with susceptibility to streptococcal cell wall-induced arthritis in Lewis rats. Proc. Natl. Acad. Sci. U.S.A. 86:4771–4775.

    PubMed  CAS  Google Scholar 

  • Strickland, I., Kisich, K., Hauk, P.J., Vottero, A., Chrousos, G.P., Klemm, D.J., and Leung, D.Y.M. (2001). High constitutive glucocorticoid receptor Î’ in human neutrophils enables them to reduce their spontaneous rate of cell death in response to corticosteroids. J. Exp. Med. 193:585–593.

    PubMed  CAS  Google Scholar 

  • Szatmary, Z., Garabedian, M.J., and Vilcek, J. (2004). Inhibition of glucocorticoid receptor-mediated transcriptional activation by p38 mitogen-activated protein (MAP) kinase. J. Biol. Chem. 279:43708–43715.

    PubMed  CAS  Google Scholar 

  • Takahasi, K.I., Fukushima, K., Sasano, H., Sasaki, I., Matsuno, S., Krozowski, Z.S., and Nagura, H. (1999). Type II 11beta-hydroxysteroid dehydrogenase expression in human colonic epithelial cells of inflammatory bowel disease. Dig. Dis. Sci. 44: 2516–2522.

    Google Scholar 

  • Thompson, B.T. (2003). Glucocorticoids and acute lung injury. Crit. Care Med. 31: S253–257.

    PubMed  CAS  Google Scholar 

  • Valledor, A.F., Hsu, L.C., Ogawa, S., Sawka-Verhelle, D., Karin, M., and Glass, C.K. (2004). Activation of liver X receptors and retinoid X receptors prevents bacterial-induced macrophage apoptosis. Proc. Natl.Acad. Sci. U.S.A. 101:17813–17818.

    PubMed  CAS  Google Scholar 

  • Valsamakis, G., Anwar, A., Tomlinson, J.W., Shackleton, C.H., McTernan, P.G., Chetty, R., Wood, P.J., Banerjee, A.K., Holder, G., Barnett, A.H., Stewart, P.M., and Kumar, S. (2004). 11beta-hydroxysteroid dehydrogenase type 1 activity in lean and obese males with type 2 diabetes mellitus. J. Clin. Endocrinol. Metab. 89:4755–4761.

    PubMed  CAS  Google Scholar 

  • Valtysdottir, S.T., Wide, L., and Hallgren, R. (2001). Low serum dehydroepiandrosterone sulfate in women with primary Sjogren’s syndrome as an isolated sign of impaired HPA axis function. J. Rheumatol. 28:1259–1265.

    PubMed  CAS  Google Scholar 

  • Vermes, I., and Beishuizen, A. (2001). The hypothalamic-pituitary-adrenal response to critical illness. Best Pract. Res. Clin. Endocrinol. Metab. 15:495–511.

    PubMed  CAS  Google Scholar 

  • Vitale, G., Pellizzari, R., Recchi, C., Napolitani, G., Mock, M., and Montecucco, C. (1998). Anthrax lethal factor cleaves the N-terminus of MAPKKs and induces tyrosine/threonine phosphorylation of MAPKs in cultured macrophages. Biochem. Biophys. Res. Commun. 248:706–711.

    PubMed  CAS  Google Scholar 

  • Vottero, A., and Chrousos, G.P. (1999). Glucocorticoid receptor Î’: View I. Trends Endocrinol. Metab. 10:333–338.

    PubMed  CAS  Google Scholar 

  • Wang, X., Wu, H., and Miller, A.H. (2004). Interleukin 1alpha (IL-1alpha) induced activation of p38 mitogen-activated protein kinase inhibits glucocorticoid receptor function. Mol. Psychiatry 9:65–75.

    PubMed  CAS  Google Scholar 

  • Watters, J.W., Dewar, K., Lehoczky, J., Boyartchuk, V., and Dietrich, W.F. (2001). Kif1c, a kinesin-like motor protein, mediates mouse macrophage resistance to anthrax lethal factor. Curr. Biol. 11:1503–1511.

    PubMed  CAS  Google Scholar 

  • Webster, J.I., and Carlstedt-Duke, J. (2002). Involvement of multidrug-resistance proteins (MDR) in the modulation of glucocorticoid response. J. Steroid Biochem. Mol. Biol. 82:277–288.

    PubMed  CAS  Google Scholar 

  • Webster, J.I., and Sternberg, E.M. (2004). Role of the hypothalamic-pituitary-adrenal axis, glucocorticoids and glucocorticoid receptors in toxic sequelae of exposure to bacterial and viral products. J. Endocrinol. 181:207–221.

    PubMed  CAS  Google Scholar 

  • Webster, J.I., and Sternberg, E.M. (2005). Anthrax lethal toxin represses glucocorticoid receptor (GR) transactivation by inhibiting GR-DNA binding in vivo. Mol. Cell. Endocrinol. 241:21–31.

    PubMed  CAS  Google Scholar 

  • Webster, J.I., Tonelli, L., and Sternberg, E.M. (2002). Neuroendocrine regulation of immunity. Annu. Rev. Immunol. 20:125–163.

    PubMed  CAS  Google Scholar 

  • Webster, J.I., Tonelli, L.H., Moayeri, M., Simons, S.S., Jr., Leppla, S.H., and Sternberg, E.M. (2003). Anthrax lethal factor represses glucocorticoid and progesterone receptor activity. Proc. Natl. Acad. Sci. U.S.A. 100:5706–5711.

    PubMed  CAS  Google Scholar 

  • Wei, T., and Lightman, S.L. (1997). The neuroendocrine axis in patients with multiple sclerosis. Brain 120:1067–1076.

    PubMed  Google Scholar 

  • Wesche, J., Elliott, J.L., Falnes, P.O., Olsnes, S., and Collier, R.J. (1998). Characterization of membrane translocation by anthrax protective antigen. Biochemistry 37: 15737–15746.

    PubMed  CAS  Google Scholar 

  • Westerbacka, J., Yki-Jarvinen, H., Vehkavaara, S., Hakkinen, A.M., Andrew, R., Wake, D.J., Seckl, J.R., and Walker, B.R. (2003). Body fat distribution and cortisol metabolism in healthy men: Enhanced 5beta-reductase and lower cortisol/cortisone metabolite ratios in men with fatty liver. J. Clin. Endocrinol. Metab. 88:4924–4931.

    PubMed  CAS  Google Scholar 

  • Wick, G., Sgonc, R., and Lechner, O. (1998). Neuroendocrine-immune disturbances in animal models with spontaneous autoimmune diseases. Ann. N. Y. Acad. Sci. 840:591–598.

    PubMed  CAS  Google Scholar 

  • Wilder, R.L., Calandra, G.B., Garvin, A.J., Wright, K.D., and Hansen, C.T. (1982). Strain and sex variation in the susceptibility to streptococcal cell wall-induced polyarthritis in the rat. Arthritis Rheum. 25:1064–1072.

    PubMed  CAS  Google Scholar 

  • Zhao, J., Milne, J.C., and Collier, R.J. (1995). Effect of anthrax toxin’s lethal factor on ion channels formed by the protective antigen. J. Biol. Chem. 270:18626–18630.

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. Jeanette I. Webster
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mahtab Moayeri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Esther M. Sternberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Departments of Veterinary Integrative Biosciences and Veterinary Pathobiology College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843-4458

    C. Jane Welsh

  2. Department of Psychology College of Liberal Arts, Texas A&M University, College Station, TX, 77843-4225

    Mary W. Meagher

  3. Section on Neuroendocrine Immunology and Behavior, National Institute of Mental Health National Institutes of Health, Rockville, MD, 20892-9401

    Esther M. Sternberg

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Webster, J.I., Moayeri, M., Sternberg, E.M. (2006). Anthrax Lethal Factor Represses Glucocorticoid and Progesterone Receptor Activity. In: Welsh, C.J., Meagher, M.W., Sternberg, E.M. (eds) Neural and Neuroendocrine Mechanisms in Host Defense and Autoimmunity. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-48334-4_4

Download citation

Publish with us

Policies and ethics

Search

Navigation