Periferní metabolismus glukokortikoidů v imunitních buňkách

• Main Author: Ergang, Peter
• Other Authors: Pácha, Jiří
• Format: Doctoral Thesis
• Language: Czech
• Published: 2013
• Online Access: http://www.nusl.cz/ntk/nusl-327231

4 Abstract Glucocorticoids are hormones that regulate a variety of homeostatic processes including metabolism, cell proliferation, differentiation and immune functions, including inflammation. Acute inflammatory response is associated with an increase in glucocorticoid levels via the stimulation of pro-inflammatory cytokines and activation of the hypothalamo- pituitary-adrenal axis. Within target cells or tissues the glucocorticoid action depends not only on the plasma level of the hormone, its receptors and receptor-effector coupling, but also on the local metabolism of glucocorticoids. Two distinct types of this enzyme have been cloned and characterized. Type 1 (11HSD1) is a NADP+ (H)-dependent enzyme whose reductase activity predominates in intact cells. This enzyme activates cortisol and corticosterone from their 11-keto derivatives and thus increases the local concentration of active glucocorticoid. In contrast, type 2 (11HSD2) requires NAD+ as a co-substrate and possesses only dehydrogenase activity, thereby inactivating endogenous glucocorticoid hormones. We have demonstrated that inflammation (arthritis or experimental colitis) is accompanied by elevated 11-reductase activity and the expression of 11HSD1 mRNA, moreover in the case of colitis also with a decrease in the expression of 11HSD2....