J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/07/189/10 $2.00
Volume 186, Number 2, July 21, 1997 189-198

Tumor Necrosis Factor  and Interleukin 1 Enhance the Cortisone/Cortisol Shuttle

By Geneviève Escher, Ivo Galli, Bannikuppe S. Vishwanath, Brigitte M. Frey, and Felix J. Frey

From the Division of Nephrology, University Hospital of Berne, 3010 Berne, Switzerland

Endogenously released or exogenously administered glucocorticosteroids are relevant hormones for controlling inflammation. Only 11-hydroxy glucocorticosteroids, but not 11-keto glucocorticosteroids, activate glucocorticoid receptors. Since we found that glomerular mesangial cells (GMC) express 11-hydroxysteroid dehydrogenase 1 (11-OHSD1), which interconverts 11-keto glucocorticosteroids into 11-hydroxy glucocorticosteroids (cortisone/cortisol shuttle), we explored whether 11-OHSD1 determines the antiinflammatory effect of glucocorticosteroids. GMC exposed to interleukin (IL)-1 or tumor necrosis factor  (TNF-) release group II phospholipase A2 (PLA2), a key enzyme producing inflammatory mediators. 11-hydroxy glucocorticosteroids inhibited cytokine-induced transcription and release of PLA2 through a glucocorticoid receptor-dependent mechanism. This inhibition was enhanced by inhibiting 11-OHSD1. Interestingly, 11-keto glucocorticosteroids decreased cytokine-induced PLA2 release as well, a finding abrogated by inhibiting 11-OHSD1. Stimulating GMC with IL-1 or TNF- increased expression and reductase activity of 11-OHSD1. Similarly, this IL-1- and TNF--induced formation of active 11-hydroxy glucocorticosteroids from inert 11-keto glucocorticosteroids by the 11-OHSD1 was shown in the Kiki cell line that expresses the stably transfected bacterial -galactosidase gene under the control of a glucocorticosteroids response element. Thus, we conclude that 11-OHSD1 controls access of 11-hydroxy glucocorticosteroids and 11-keto glucocorticosteroids to glucocorticoid receptors and thus determines the anti-inflammatory effect of glucocorticosteroids. IL-1 and TNF- upregulate specifically the reductase activity of 11-OHSD1 and counterbalance by that mechanism their own proinflammatory effect.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• D'Elia, M., Patenaude, J., Bernier, J. (2009). Regulation of glucocorticoid sensitivity in thymocytes from burn-injured mice. Am. J. Physiol. Endocrinol. Metab. 296: E97-E104 [Abstract] [Full Text]  
• Buttgereit, F., Zhou, H., Seibel, M. J (2008). Arthritis and endogenous glucocorticoids: the emerging role of the 11{beta}-HSD enzymes. Ann Rheum Dis 67: 1201-1203 [Full Text]  
• Fegan, K S, Rae, M T, Critchley, H O D, Hillier, S G (2008). Anti-inflammatory steroid signalling in the human peritoneum. J Endocrinol 196: 369-376 [Abstract] [Full Text]  
• Balazs, Z., Schweizer, R. A.S., Frey, F. J., Rohner-Jeanrenaud, F., Odermatt, A. (2008). DHEA Induces 11 -HSD2 by Acting on CCAAT/Enhancer-Binding Proteins. J. Am. Soc. Nephrol. 19: 92-101 [Abstract] [Full Text]  
• Cooper, M. S., Stewart, P. M. (2007). Adrenal Insufficiency in Critical Illness. J Intensive Care Med 22: 348-362 [Abstract]  
• Alikhani-Koupaei, R., Fouladkou, F., Fustier, P., Cenni, B., Sharma, A. M., Deter, H.-C., Frey, B. M., Frey, F. J. (2007). Identification of polymorphisms in the human 11beta-hydroxysteroid dehydrogenase type 2 gene promoter: functional characterization and relevance for salt sensitivity. FASEB J. 21: 3618-3628 [Abstract] [Full Text]  
• Hillier, S. G (2007). Diamonds are forever: the cortisone legacy. J Endocrinol 195: 1-6 [Abstract] [Full Text]  
• Lee, H.-Y., Acosta, T. J, Tanikawa, M., Sakumoto, R., Komiyama, J., Tasaki, Y., Piskula, M., Skarzynski, D. J, Tetsuka, M., Okuda, K. (2007). The role of glucocorticoid in the regulation of prostaglandin biosynthesis in non-pregnant bovine endometrium. J Endocrinol 193: 127-135 [Abstract] [Full Text]  
• Dover, A. R., Hadoke, P. W. F., Macdonald, L. J., Miller, E., Newby, D. E., Walker, B. R. (2007). Intravascular Glucocorticoid Metabolism during Inflammation and Injury in Mice. Endocrinology 148: 166-172 [Abstract] [Full Text]  
• Vagnerova, K, Kverka, M, Klusonova, P, Ergang, P, Miksik, I, Tlaskalova-Hogenova, H, Pacha, J (2006). Intestinal inflammation modulates expression of 11{beta}-hydroxysteroid dehydrogenase in murine gut.. J Endocrinol 191: 497-503 [Abstract] [Full Text]  
• Gilmour, J. S., Coutinho, A. E., Cailhier, J.-F., Man, T. Y., Clay, M., Thomas, G., Harris, H. J., Mullins, J. J., Seckl, J. R., Savill, J. S., Chapman, K. E. (2006). Local amplification of glucocorticoids by 11beta-hydroxysteroid dehydrogenase type 1 promotes macrophage phagocytosis of apoptotic leukocytes.. J. Immunol. 176: 7605-7611 [Abstract] [Full Text]  
• Bruley, C., Lyons, V., Worsley, A. G. F., Wilde, M. D., Darlington, G. D., Morton, N. M., Seckl, J. R., Chapman, K. E. (2006). A Novel Promoter for the 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Gene Is Active in Lung and Is C/EBP{alpha} Independent. Endocrinology 147: 2879-2885 [Abstract] [Full Text]  
• Kossintseva, I., Wong, S., Johnstone, E., Guilbert, L., Olson, D. M., Mitchell, B. F. (2006). Proinflammatory cytokines inhibit human placental 11{beta}-hydroxysteroid dehydrogenase type 2 activity through Ca2+ and cAMP pathways. Am. J. Physiol. Endocrinol. Metab. 290: E282-E288 [Abstract] [Full Text]  
• Kadereit, B., Fustier, P., Shojaati, K., Frey, B. M., Frey, F. J., Mohaupt, M. G. (2005). Extracellular ATP Determines 11{beta}-Hydroxysteroid Dehydrogenase Type 2 Activity via Purinergic Receptors. J. Am. Soc. Nephrol. 16: 3507-3516 [Abstract] [Full Text]  
• Freeman, L., Hewison, M., Hughes, S. V., Evans, K. N., Hardie, D., Means, T. K., Chakraverty, R. (2005). Expression of 11{beta}-hydroxysteroid dehydrogenase type 1 permits regulation of glucocorticoid bioavailability by human dendritic cells. Blood 106: 2042-2049 [Abstract] [Full Text]  
• Johnstone, J. F., Bocking, A. D., Unlugedik, E., Challis, J. R.G. (2005). The Effects of Chorioamnionitis and Betamethasone on 11{beta}, Hydroxysteroid Dehydrogenase Types 1 and 2 and the Glucocorticoid Receptor in Preterm Human Placenta. Reproductive Sciences 12: 238-245 [Abstract]  
• Gubbay, O, Guo, W, Rae, M T, Niven, D, Howie, A F, McNeilly, A S, Xu, L, Hillier, S G (2004). Anti-inflammatory and proliferative responses in human and ovine ovarian surface epithelial cells. Reproduction 128: 607-614 [Abstract] [Full Text]  
• Tomlinson, J. W., Walker, E. A., Bujalska, I. J., Draper, N., Lavery, G. G., Cooper, M. S., Hewison, M., Stewart, P. M. (2004). 11{beta}-Hydroxysteroid Dehydrogenase Type 1: A Tissue-Specific Regulator of Glucocorticoid Response. Endocr. Rev. 25: 831-866 [Abstract] [Full Text]  
• Rae, M. T., Niven, D., Critchley, H. O. D., Harlow, C. R., Hillier, S. G. (2004). Antiinflammatory Steroid Action in Human Ovarian Surface Epithelial Cells. J. Clin. Endocrinol. Metab. 89: 4538-4544 [Abstract] [Full Text]  
• Cheron, A., Peltier, J., Perez, J., Bellocq, A., Fouqueray, B., Baud, L. (2004). 15-Deoxy-{Delta}12,14-Prostaglandin J2 Inhibits Glucocorticoid Binding and Signaling in Macrophages through a Peroxisome Proliferator-Activated Receptor {gamma}-Independent Process. J. Immunol. 172: 7677-7683 [Abstract] [Full Text]  
• Justesen, J., Mosekilde, L., Holmes, M., Stenderup, K., Gasser, J., Mullins, J. J., Seckl, J. R., Kassem, M. (2004). Mice Deficient in 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Lack Bone Marrow Adipocytes, but Maintain Normal Bone Formation. Endocrinology 145: 1916-1925 [Abstract] [Full Text]  
• Kondrack, R. M., Harbertson, J., Tan, J. T., McBreen, M. E., Surh, C. D., Bradley, L. M. (2003). Interleukin 7 Regulates the Survival and Generation of Memory CD4 Cells. JEM 198: 1797-1806 [Abstract] [Full Text]  
• Rauz, S., Cheung, C.M.G., Wood, P.J., Coca-Prados, M., Walker, E.A., Murray, P.I., Stewart, P.M. (2003). Inhibition of 11{beta}-hydroxysteroid dehydrogenase type 1 lowers intraocular pressure in patients with ocular hypertension. QJM 96: 481-490 [Abstract] [Full Text]  
• Friedberg, M., Zoumakis, E., Hiroi, N., Bader, T., Chrousos, G. P., Hochberg, Z.'e. (2003). Modulation of 11{beta}-Hydroxysteroid Dehydrogenase Type 1 in Mature Human Subcutaneous Adipocytes by Hypothalamic Messengers. J. Clin. Endocrinol. Metab. 88: 385-393 [Abstract] [Full Text]  
• Yong, P. Y.K., Harlow, C., Thong, K.J., Hillier, S. G. (2002). Regulation of 11{beta}-hydroxysteroid dehydrogenase type 1 gene expression in human ovarian surface epithelial cells by interleukin-1. Hum Reprod 17: 2300-2306 [Abstract] [Full Text]  
• Vogt, B., Dick, B., Marti, H.-P., Frey, F. J., Frey, B. M. (2002). Reduced 11{beta}-hydroxysteroid dehydrogenase activity in experimental nephrotic syndrome. Nephrol Dial Transplant 17: 753-758 [Abstract] [Full Text]  
• Nawrocki, A. R., Goldring, C. E., Kostadinova, R. M., Frey, F. J., Frey, B. M. (2002). In Vivo Footprinting of the Human 11beta -Hydroxysteroid Dehydrogenase Type 2 Promoter. EVIDENCE FOR CELL-SPECIFIC REGULATION BY Sp1 AND Sp3. J. Biol. Chem. 277: 14647-14656 [Abstract] [Full Text]  
• Whorwood, C. B., Donovan, S. J., Flanagan, D., Phillips, D. I.W., Byrne, C. D. (2002). Increased Glucocorticoid Receptor Expression in Human Skeletal Muscle Cells May Contribute to the Pathogenesis of the Metabolic Syndrome. Diabetes 51: 1066-1075 [Abstract] [Full Text]  
• Serra, A., Uehlinger, D. E., Ferrari, P., Dick, B., Frey, B. M., Frey, F. J., Vogt, B. (2002). Glycyrrhetinic Acid Decreases Plasma Potassium Concentrations in Patients with Anuria. J. Am. Soc. Nephrol. 13: 191-196 [Abstract] [Full Text]  
• Johansson, A., Andrew, R., Forsberg, H., Cederquist, K., Walker, B. R., Olsson, T. (2001). Glucocorticoid Metabolism and Adrenocortical Reactivity to ACTH in Myotonic Dystrophy. J. Clin. Endocrinol. Metab. 86: 4276-4283 [Abstract] [Full Text]  
• Thieringer, R., Le Grand, C. B., Carbin, L., Cai, T.-Q., Wong, B., Wright, S. D., Hermanowski-Vosatka, A. (2001). 11{{beta}}-Hydroxysteroid Dehydrogenase Type 1 Is Induced in Human Monocytes upon Differentiation to Macrophages. J. Immunol. 167: 30-35 [Abstract] [Full Text]  
• Zhang, H. H., Kumar, S., Barnett, A. H., Eggo, M. C. (2001). Dexamethasone Inhibits Tumor Necrosis Factor-{{alpha}}-Induced Apoptosis and Interleukin-1{beta} Release in Human Subcutaneous Adipocytes and Preadipocytes. J. Clin. Endocrinol. Metab. 86: 2817-2825 [Abstract] [Full Text]  
• Whorwood, C. B., Donovan, S. J., Wood, P. J., Phillips, D. I. W. (2001). Regulation of Glucocorticoid Receptor {{alpha}} and {beta} Isoforms and Type I 11{beta}-Hydroxysteroid Dehydrogenase Expression in Human Skeletal Muscle Cells: A Key Role in the Pathogenesis of Insulin Resistance?. J. Clin. Endocrinol. Metab. 86: 2296-2308 [Abstract] [Full Text]  
• Tomlinson, J. W., Moore, J., Cooper, M. S., Bujalska, I., Shahmanesh, M., Burt, C., Strain, A., Hewison, M., Stewart, P. M. (2001). Regulation of Expression of 11{beta}-Hydroxysteroid Dehydrogenase Type 1 in Adipose Tissue: Tissue-Specific Induction by Cytokines. Endocrinology 142: 1982-1989 [Abstract] [Full Text]  
• Rook, G.A.W., Seah, G., Ustianowski, A. (2001). M. tuberculosis: immunology and vaccination. Eur Respir J 17: 537-557 [Abstract] [Full Text]  
• Odermatt, A., Dick, B., Arnold, P., Zaehner, T., Plueschke, V., Deregibus, M. N., Repetto, H., Frey, B. M., Frey, F. J., Ferrari, P. (2001). A Mutation in the Cofactor-Binding Domain of 11{beta}-Hydroxysteroid Dehydrogenase Type 2 Associated with Mineralocorticoid Hypertension. J. Clin. Endocrinol. Metab. 86: 1247-1252 [Abstract] [Full Text]  
• Lanz, C.-B., Causevic, M., Heiniger, C., Frey, F. J., Frey, B. M., Mohaupt, M. G. (2001). Fluid Shear Stress Reduces 11{beta}-Hydroxysteroid Dehydrogenase Type 2. Hypertension 37: 160-169 [Abstract] [Full Text]  
• Yong, P. Y. K., Thong, K. J., Andrew, R., Walker, B. R., Hillier, S. G. (2000). Development-Related Increase in Cortisol Biosynthesis by Human Granulosa Cells. J. Clin. Endocrinol. Metab. 85: 4728-4733 [Abstract] [Full Text]  
• BAKER, R. W., WALKER, B. R., SHAW, R. J., HONOUR, J. W., JESSOP, D. S., LIGHTMAN, S. L., ZUMLA, A., ROOK, G. A. W. (2000). Increased Cortisol . Cortisone Ratio in Acute Pulmonary Tuberculosis. Am. J. Respir. Crit. Care Med. 162: 1641-1647 [Abstract] [Full Text]  
• Frey, F. J., Ferrari, P. (2000). Pastis and hypertension--what is the molecular basis?. Nephrol Dial Transplant 15: 1512-1514 [Full Text]  
• Waddell, B. J., Burton, P. J. (2000). Full Induction of Rat Myometrial 11{beta}-Hydroxysteroid Dehydrogenase Type 1 in Late Pregnancy Is Dependent on Intrauterine Occupancy. Biol. Reprod. 62: 1005-1009 [Abstract] [Full Text]  
• Livingstone, D. E. W., Jones, G. C., Smith, K., Jamieson, P. M., Andrew, R., Kenyon, C. J., Walker, B. R. (2000). Understanding the Role of Glucocorticoids in Obesity: Tissue-Specific Alterations of Corticosterone Metabolism in Obese Zucker Rats. Endocrinology 141: 560-563 [Abstract] [Full Text]  
• FREY, B. M., REBER, B. F. X., VISHWANATH, B. S., ESCHER, G., FREY, F. J. (1999). Annexin I modulates cell functions by controlling intracellular calcium release. FASEB J. 13: 2235-2245 [Abstract] [Full Text]  
• Odermatt, A., Arnold, P., Stauffer, A., Frey, B. M., Frey, F. J. (1999). The N-terminal Anchor Sequences of 11beta -Hydroxysteroid Dehydrogenases Determine Their Orientation in the Endoplasmic Reticulum Membrane. J. Biol. Chem. 274: 28762-28770 [Abstract] [Full Text]  
• Finken, M. J. J., Andrews, R. C., Andrew, R., Walker, B. R. (1999). Cortisol Metabolism in Healthy Young Adults: Sexual Dimorphism in Activities of A-Ring Reductases, but not 11{beta}-Hydroxysteroid Dehydrogenases. J. Clin. Endocrinol. Metab. 84: 3316-3321 [Abstract] [Full Text]  
• Fuster, D., Escher, G., Vogt, B., Ackermann, D., Dick, B., Frey, B. M., Frey, F. J. (1998). Furosemide Inhibits 11{beta}-Hydroxysteroid Dehydrogenase Type 2. Endocrinology 139: 3849-3854 [Abstract] [Full Text]  
• Escher, G., Vogt, B., Beck, T., Guntern, D., Frey, B. M., Frey, F. J. (1998). Reduced 11{beta}-Hydroxysteroid Dehydrogenase Activity in the Remaining Kidney Following Nephrectomy. Endocrinology 139: 1533-1539 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS