期刊
STEROIDS
卷 74, 期 4-5, 页码 449-455出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.steroids.2008.12.013
关键词
Fish; Cortisol; Phagocytosis; Non-genomic action
资金
- Council of Scientific and Industrial Research, India
- Indian Council of Agricultural Research, New Delhi, India
The non-genomic action of glucocorticoid, besides classical genomic action, is recently implicated in regulation of phagocyte activities in mammals. With regard to the non-mammalian vertebrates, this study in the teleost, Channa punctatus, for the first time demonstrates the regulation of innate immunity by cortisol following non-genomic pathway. Cortisol suppressed the phagocytic activity of splenic phagocytes in a time- and concentration-dependent manner. Intriguingly, it impeded the phagocytosis within 15 min which is too short for conventional genomic action. The cortisol-induced rapid inhibition could not be altered by transcription and translation inhibitors, suggesting the involvement of non-genomic pathway. Since membrane impermeable BSA-cortisol mimicked the rapid inhibitory effect of cortisol at 15 min, we speculated that cortisol exerted its non-genomic effect on phagocytosis by acting at membrane site. These membrane-bound glucocorticoid receptors seem similar to cytosolic GR, as rapid inhibitory effect of cortisol was blocked by the cyroplasmic glucocorticoid receptor blocker RU-486. Using inhibitors for adenylate cyclase/protein kinase A (PKA) and estimating intracellular cAMP, adenylate cyclase-PKA pathway was seen involved in mediating the rapid non-genomic action of cortisol in phagocytes of C. punctatus. In contrast to the rapid effect, inhibitory effect of cortisol oil phagocytosis after 1 h was blocked by protein synthesis inhibitors, thus implicating genomic regulation. An overview of our data suggests that cortisol regulates phagocyrosis in C. punctatus via genomic as well as non-genomic mechanisms. Further, the non-genomic action of cortisol is mediated via membrane-bound GR Coupled to cAMP-PKA system. (C) 2008 Elsevier Inc. All rights reserved.
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