Genomic and non-genomic effect of cortisol on phagocytosis in freshwater teleost Channa punctatus: An in vitro study

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 cytoplasmic 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 on phagocytosis after 1 h was blocked by protein synthesis inhibitors, thus implicating genomic regulation. An overview of our data suggests that cortisol regulates phagocytosis 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.