Pro-opiomelanocortin-derived peptides induce IL-10 production in human monocytes.
There is strong evidence for the existence of a neuroimmune axis which is regulated by a network of interacting cytokines and neuropeptides. Accordingly, pro-opiomelanocortin-derived peptide hormones such as melanocyte-stimulating hormones (MSH), adrenocorticotropin, and beta-endorphin not only could be detected in many immunocompetent cells but also turned out to be potent immunomodulating and anti-inflammatory mediators, mainly through regulating cytokine production. Thus, it was investigated whether alpha-MSH, which is known to inhibit immune and inflammatory responses, would influence the production of the cytokine synthesis inhibitor IL-10 by human PBMC. Stimulation of PBMC with alpha-MSH resulted in a significantly enhanced release of, IL-10 protein. These data were confirmed by Northern blot analysis, which demonstrated increased IL-10 mRNA expression induced by alpha-MSH. This effect of alpha-MSH was dose-dependent; maximum IL-10 release and mRNA expression were obtained at a concentration of 10(-13) M. There is also clear evidence that only the C-terminal tripeptide of alpha-MSH was required to enhance IL-10 production. In addition, alpha-MSH and its tripeptide strongly induced IL-10 in purified monocytes. In contrast, neither unstimulated nor activated T lymphocytes produced increased amounts of IL-10 in response to alpha-MSH. These findings indicate that pro-opiomelanocortin peptides such as alpha-MSH are able to up-regulate the production of suppressor factors such as IL-10 in monocytes and thereby may contribute to immunosuppression.
Bhardwaj
R S
RS
Ludwig Boltzmann Insitute for Cell Biology and Immunobiology of the Skin, Department of Dermatology, University of Münster, Germany.
Schwarz
A
A
Becher
E
E
Mahnke
K
K
Aragane
Y
Y
Schwarz
T
T
Luger
T A
TA
D000595:Amino Acid Sequence; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology*; D010446:Peptide Fragments / Q000235:genetics / Q000494:pharmacology; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation; D000521:alpha-MSH / Q000235:genetics / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D010446:Peptide Fragments; D012333:RNA, Messenger; D016753:Interleukin-10; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin