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Short-chain fatty acids act as antiinflammatory mediators by regulating prostaglandin e_2 and cytokines

World Journal of Gastroenterology 2009年第44期15卷 5549-5557页

作者： Mary Ann Cox James Jackson Michaela Stanton Alberto Rojas-Triana Loretta Bober Maureen Laverty Xiaoxin Yang Feng Zhu Jianjun Liu Suke Wang fre.e.ick monsma Galya Vassileva Maureen Maguire eric Gustafson Marvin Bayne Chuan-Chu Chou Daniel Lundell Chung-Her Jenh Department of Tumor Biology Schering-Plough Research Institute Kenilworth NJ 07033 United States Department of Cardiovascular and Metabolic Disease Research Schering-Plough Research Institute Kenilworth NJ 07033 United States Department of Discovery Technologies Schering-Plough Research Institute Kenilworth NJ 07033 United States Department of Discovery Technologies Schering- Plough Research Institute Kenilworth NJ 07033 United States Department of Inflammation Schering-Plough Research Institute Kenilworth NJ 07033 United States

AIM： To investigate the effect of short-chain fatty acids （SCFAs） on production of prostaglandin e2 （PGe2）, cytokines and chemokines in human monocytes. MeTHODS： Human neutrophils and monocytes were isolated from human whole blood by using 1-Step Polymorph and RosetteSep Human Monocyte enrichment Cocktail, respectively. Human GPR41 and GPR43 mRNA expression was examined by quantitative realtime polymerase chain reaction, The calcium flux assay was used to examine the biological activities of SCFAs in human neutrophils and monocytes. The effect of SCFAs on human monocytes and peripheral blood mononuclear cells （PBMC） was studied by measuring PGe2, cytokines and chemokines in the supernatant. The effect of SCFAs in vivo was examined by intraplantar injection into rat paws. ReSULTS： Human GPR43 is highly expressed in human neutrophils and monocytes. SCFAs induce robust calcium flux in human neutrophils, but not in human monocytes. In this study, we show that SCFAs can induce human monocyte release of PGe2 and that this effect can be enhanced in the presence of lipopolysaccharide （LPS）. In addition, we demonstrate that PGe2 production induced by SCFA was inhibited by pertussis toxin, suggesting the involvement of a receptor-mediated mechanism. Furthermore, SCFAs can specifically inhibit constitutive monocyte chemotactic protein-1 （MCP-1） production and LPS-induced interleukin-10 （IL-10） production in human monocytes without affecting the secretion of other cytokines and chemokines examined. Similar activities were observed in human PBMC for the release of PGe2, MCP-1 and IL-10 after 5CFA treatment. In addition, SCFAs inhibit LPS-induced production of tumor necrosis factor-α and interferon-7 in human PBIVlC. Finally, we show that SCFAs and LPS can induce PGe2 production in vivo by intraplantar injection into rat paws （P 〈 0.01）. CONCLUSION： SCFAs can have distinct antiinflammatory activities due to their regulation of PGe2, cytokine and chemokine release from human

关键词： Short-chain fatty acids GPR43 GPR41 Human monocytes Prostaglandin e2 Chemokines Cytokines

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