Brief Article
Copyright ©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Nov 28, 2009; 15(44): 5549-5557
Published online Nov 28, 2009. doi: 10.3748/wjg.15.5549
Short-chain fatty acids act as antiinflammatory mediators by regulating prostaglandin E2 and cytokines
Mary Ann Cox, James Jackson, Michaela Stanton, Alberto Rojas-Triana, Loretta Bober, Maureen Laverty, Xiaoxin Yang, Feng Zhu, Jianjun Liu, Suke Wang, Frederick Monsma, Galya Vassileva, Maureen Maguire, Eric Gustafson, Marvin Bayne, Chuan-Chu Chou, Daniel Lundell, Chung-Her Jenh
Mary Ann Cox, Department of Tumor Biology, Schering-Plough Research Institute, Kenilworth, NJ 07033, United States
James Jackson, Michaela Stanton, Alberto Rojas-Triana, Loretta Bober, Marvin Bayne, Chuan-Chu Chou, Chung-Her Jenh, Department of Cardiovascular and Metabolic Disease Research, Schering-Plough Research Institute, Kenilworth, NJ 07033, United States
Maureen Laverty, Xiaoxin Yang, Feng Zhu, Jianjun Liu, Suke Wang, Frederick Monsma, Galya Vassileva, Maureen Maguire, Eric Gustafson, Department of Discovery Technologies, Schering-Plough Research Institute, Kenilworth, NJ 07033, United States
Marvin Bayne, Department of Discovery Technologies, Schering-Plough Research Institute, Kenilworth, NJ 07033, United States
Daniel Lundell, Department of Inflammation, Schering-Plough Research Institute, Kenilworth, NJ 07033, United States
Author contributions: Cox MA, Jackson J, Stanton M, Rojas-Triana A, Laverty M, Yang X, Zhu F, Liu J and Maguire M performed the research; Cox MA, Bober L, Wang S, Monsma F, Vassileva G, Gustafson E and Jenh CH designed the research; Bayne M, Chou CC and Lundell D provided support and critical reading; Bober L contributed to the writing and discussion; Jenh CH coordinated the research and wrote the manuscript.
Correspondence to: Dr. Chung-Her Jenh, Department of Cardiovascular and Metabolic Disease Research, Schering-Plough Research Institute, K-15-1600, 2015 Galloping Hill Road, Kenilworth, NJ 07033, United States. chung-her.jenh@spcorp.com
Telephone: +1-908-7403072 Fax: +1-908-7407115
Received: August 14, 2009
Revised: September 12, 2009
Accepted: September 19, 2009
Published online: November 28, 2009
Abstract

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 real-time 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 SCFA treatment. In addition, SCFAs inhibit LPS-induced production of tumor necrosis factor-α and interferon-γ in human PBMC. 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 immune cells.

Keywords: Short-chain fatty acids, GPR43, GPR41, Human monocytes, Prostaglandin E2, Chemokines, Cytokines