α‐Melanocyte‐stimulating hormone inhibits lipopolysaccharide‐induced biological responses by downregulating CD14 from macrophages

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Abstract
Monocytes/macrophages are the first cells involved in inflammation. α-Melanocyte-stimulating hormone (α-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 α-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. α-MSH also inhibited SA-LPS-induced nuclear transcription factor κB activation not only in macrophages, but also in a T-cell line and human neutrophils isolated from fresh blood. α-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 α-MSH-mediated downregulation of CD14. Overall, our results suggest that α-MSH exerts its anti-inflammatory effect by a novel mechanism in macrophages through downregulating of the endotoxin receptor CD14