AJP - Regulatory, Integrative and Comparative Physiology, Vol 270, Issue 6 1296-R1306, Copyright © 1996 by American Physiological Society

ARTICLES

11 beta-hydroxysteroid dehydrogenase modulation of glucocorticoid activities in lymphoid organs

J. D. Hennebold, S. Y. Ryu, H. H. Mu, A. Galbraith and R. A. Daynes
Department of Pathology, University of Utah School of Medicine, Salt Lake City 84132, USA.

The immunoregulatory effects of glucocorticoids (GCS) are linked to their capacity to alter the production of various species of cytokines associated with immune and inflammatory processes. The present study determined that the influences of GCS within particular lymphoid organs vary, depending on the specific activity of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) within the tissue. This enzyme converts active GCS to inactive metabolites and was found to display greater activity in peripheral than in mucosal lymphoid organs. A direct correlation was found between 11 beta-HSD activity and the preferential production of type 1 cytokines by T-cells residing within certain lymphoid organs. It was established that lymphoid organ 11 beta-HSD was localized in the immobile stromal cell components. Inhibition of 11 beta-HSD activity in vivo reduced type 1 and enhanced type 2 cytokine production by activated T-cells, and it also depressed the ability of animals to generate contact hypersensitivity responses. We conclude that GCS levels can be controlled within lymphoid organs through oxidative inactivation by 11 beta-HSD. GCS action is, therefore, dependent on tissue levels of 11 beta-HSD activity, the number of GCS receptors in a responsive cell, and the concentration of circulating GCS.

This article has been cited by other articles:

				R. Thieringer, C. B. Le Grand, L. Carbin, T.-Q. Cai, B. Wong, S. D. Wright, and A. Hermanowski-Vosatka 11{{beta}}-Hydroxysteroid Dehydrogenase Type 1 Is Induced in Human Monocytes upon Differentiation to Macrophages J. Immunol., July 1, 2001; 167(1): 30 - 35. [Abstract] [Full Text] [PDF]

				H. Horigome, A. Horigome, M. Homma, T. Hirano, and K. Oka Glycyrrhetinic acid-induced apoptosis in thymocytes: impact of 11beta -hydroxysteroid dehydrogenase inhibition Am J Physiol Endocrinol Metab, October 1, 1999; 277(4): E624 - E630. [Abstract] [Full Text] [PDF]

				K. E. Sheppard, K. X. Z. Li, and D. J. Autelitano Corticosteroid receptors and 11beta -hydroxysteroid dehydrogenase isoforms in rat intestinal epithelia Am J Physiol Gastrointest Liver Physiol, September 1, 1999; 277(3): G541 - G547. [Abstract] [Full Text] [PDF]

				K. E. Sheppard, K. Khoo, Z. S. Krozowski, and K. X. Z. Li Steroid specificity of the putative DHB receptor: evidence that the receptor is not 11beta HSD Am J Physiol Endocrinol Metab, July 1, 1998; 275(1): E124 - E131. [Abstract] [Full Text] [PDF]

				D. C. Jones, X. Ding, and R. A. Daynes Nuclear Receptor Peroxisome Proliferator-activated Receptor alpha (PPARalpha ) Is Expressed in Resting Murine Lymphocytes. THE PPARalpha IN T AND B LYMPHOCYTES IS BOTH TRANSACTIVATION AND TRANSREPRESSION COMPETENT J. Biol. Chem., February 22, 2002; 277(9): 6838 - 6845. [Abstract] [Full Text] [PDF]