α-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 a-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 I 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. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.