Differential regulation of interleukin-1 receptor antagonist by proopiomelanocortin peptides adrenocorticotropic hormone and beta-endorphin.
We have previously described the regulation of interleukin-1 receptor antagonist (IL-1ra) protein secretion and expression by IL-1, glucocorticoids and corticotropin-releasing hormone in monocytes in culture. In the present work, we analyze the direct effect of adrenocorticotropic hormone (ACTH) and beta-endorphin on the expression and secretion of IL-1ra by human monocytes in culture. ACTH exerted a dose-dependent inhibitory effect on lipopolysaccharide (LPS)-induced IL-1ra production and mRNA expression. Basal IL-1ra levels were not affected by treatment with any ACTH dose. In contrast, on human monocytes, beta-endorphin at concentrations as low as 10 pg/ml produced an increase of basal IL-1ra protein secretion and mRNA expression, this effect being reverted by pretreatment with naloxone. No effect of beta-endorphin was observed either in IL-1ra mRNA expression or protein secretion when cells were treated with LPS. The different effects of ACTH and beta-endorphin could account for their differential contribution to the inflammatory response: while ACTH contributes to the glucocorticoid overall control of the inflammatory response, beta-endorphin exerts an inhibitory tone on the resting IL-1 system. Because IL-1ra is essential in setting the level of monocyte and inflammatory response its differential regulation by the HPA axis hormones contributes to regulating the IL-1/inflammatory temporal response.
Kovalovsky
D
D
Laboratorio de Fisiología y Biología Molecular, Departamento de Biología, FCEN, Universidad de Buenos Aires, Argentina.
Pereda
M P
MP
Stalla
G K
GK
Holsboer
F
F
Arzt
E
E
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D015152:Blotting, Northern; D002478:Cells, Cultured; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000494:pharmacology*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D012795:Sialoglycoproteins / Q000378:metabolism*; D001615:beta-Endorphin / Q000494:pharmacology*
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone