Evidence of autocrine modulation of macrophage nitric oxide synthase by α-melanocyte-stimulating hormone

Robert A. Star, Nilum Rajora, Jijing Huang, Renee C. Stock, Anna Catania, J. M. Lipton

Research output: Contribution to journalArticle

Abstract

α-Melanocyte-stimulating hormone (α-MSH) is a potent inhibitory agent in all major forms of inflammation. To identify a potential mechanism of antiinflammatory action of α-MSH, we tested its effects on production of nitric oxide (NO), believed to be a mediator common to all forms of inflammation. We measured NO and α-MSH production in RAW 264.7 cultured routine macrophages stimulated with bacterial lipopolysaccharide and interferon γ. α-MSH inhibited production of NO, as estimated from nitrite production and nitration of endogenous macrophage proteins. This occurred through inhibition of production of NO synthase II protein; steady-state NO synthase II mRNA abundance was also reduced. α-MSH increased cAMP accumulation in RAW cells, characteristic of α-MSH receptors in other cell types. RAW cells also expressed mRNA for the primary α-MSH receptor (melanocortin 1). mRNA for prooplomelanocortin, the precursor molecule of α- MSH, was expressed in RAW cells, and tumor necrosis factor α increased production and release of α-MSH. These results suggest that the proinflammatory cytokine tumor necrosis factor a can induce macrophages to increase production of α-MSH, which then becomes available to act upon melanocortin receptors on the same cells. Such stimulation of melanocortin receptors could modulate inflammation by inhibiting the production of the results suggest that α-MSH is an autocrine factor in macrophages which modulates inflammation by counteracting the effects of proinflammatory cytokines.

Original languageEnglish
Pages (from-to)8016-8020
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number17
DOIs
Publication statusPublished - Aug 15 1995

Keywords

  • cAMP
  • inflammation
  • lipopolysaccharide
  • melanocortin receptors
  • tumor necrosis factor α

ASJC Scopus subject areas

  • Genetics
  • General

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