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 1h 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.
Roy
Brototi
B
Department of Zoology, University of Delhi, Delhi 110 007, India.
Rai
Umesh
U
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002417:Cattle; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004963:Estrenes / Q000494:pharmacology; D005618:Fresh Water; D016678:Genome / Q000235:genetics*; D006854:Hydrocortisone / Q000494:pharmacology*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D010473:Perciformes / Q000235:genetics* / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects*; D014176:Protein Biosynthesis / Q000187:drug effects; D011760:Pyrrolidinones / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D000067956:Adenylyl Cyclase Inhibitors; D004963:Estrenes; D007546:Isoquinolines; D011760:Pyrrolidinones; D011965:Receptors, Glucocorticoid; D013449:Sulfonamides; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C017759:9-(tetrahydro-2-furyl)-adenine; D003609:Dactinomycin; D012710:Serum Albumin, Bovine; D015735:Mifepristone; D003513:Cycloheximide; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D010738:Type C Phospholipases; D019311:Staurosporine; D000225:Adenine; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D006854:Hydrocortisone