alpha-Melanocyte-stimulating hormone inhibits lipopolysaccharide-induced biological responses by downregulating CD14 from macrophages.
Monocytes/macrophages are the first cells involved in inflammation. alpha-Melanocyte-stimulating hormone (alpha-MSH) is known to possess an anti-inflammatory role induced by a variety of stimuli; however, the molecular mechanisms underlying these effects are not clearly defined. In this report we provide evidence that alpha-MSH inhibited serum-activated lipopolysaccharide (SA-LPS)-induced proteolytic enzyme release, oxidative burst response, reactive oxygen intermediate generation, nitric oxide production, and adhesion molecule expression in monocyte-derived macrophages. alpha-MSH also inhibited SA-LPS-induced nuclear transcription factor kappaB activation not only in macrophages, but also in a T-cell line and human neutrophils isolated from fresh blood. alpha-MSH downregulated CD14, but not interleukin-1 receptor, tumor necrosis factor receptor 1 or 2 from the surface of macrophages. Anti-CD14 antibody was unable to protect alpha-MSH-mediated downregulation of CD14. Overall, our results suggest that alpha-MSH exerts its anti-inflammatory effect by a novel mechanism in macrophages through downregulating of the endotoxin receptor CD14.
Laboratory of Immunology, Centre for DNA Fingerprinting and Diagnostics, Nacharam, 500 076 Hyderabad, India.
Abira
A
Sarkar
Yashin
Y
Sreenivasan
Sunil K
SK
Manna
D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015536:Down-Regulation; D004347:Drug Interactions; D006367:HeLa Cells; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D019169:Jurkat Cells; D018950:Lipopolysaccharide Receptors / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D041681:NIH 3T3 Cells; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured; D020298:U937 Cells; D000521:alpha-MSH / Q000494:pharmacology*
D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D009569:Nitric Oxide; D000521:alpha-MSH; D000469:Alkaline Phosphatase