title: Short-chain fatty acids act as antiinflammatory mediators by regulating prostaglandin E(2) and cytokines.
abstract: OBJECTIVE
  To investigate the effect of short-chain fatty acids (SCFAs) on production of prostaglandin E(2) (PGE(2)), 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 PGE(2), 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 PGE(2) and that this effect can be enhanced in the presence of lipopolysaccharide (LPS). In addition, we demonstrate that PGE(2) 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 PGE(2), MCP-1 and IL-10 after SCFA treatment. In addition, SCFAs inhibit LPS-induced production of tumor necrosis factor-alpha and interferon-gamma in human PBMC. Finally, we show that SCFAs and LPS can induce PGE(2) production in vivo by intraplantar injection into rat paws (P < 0.01).
  
  
  CONCLUSIONS
  SCFAs can have distinct antiinflammatory activities due to their regulation of PGE(2), cytokine and chemokine release from human immune cells.
authors: Department of Tumor Biology, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
authors: Mary Ann
authors: MA
authors: Cox
authors: James
authors: J
authors: Jackson
authors: Michaela
authors: M
authors: Stanton
authors: Alberto
authors: A
authors: Rojas-Triana
authors: Loretta
authors: L
authors: Bober
authors: Maureen
authors: M
authors: Laverty
authors: Xiaoxin
authors: X
authors: Yang
authors: Feng
authors: F
authors: Zhu
authors: Jianjun
authors: J
authors: Liu
authors: Suke
authors: S
authors: Wang
authors: Frederick
authors: F
authors: Monsma
authors: Galya
authors: G
authors: Vassileva
authors: Maureen
authors: M
authors: Maguire
authors: Eric
authors: E
authors: Gustafson
authors: Marvin
authors: M
authors: Bayne
authors: Chuan-Chu
authors: CC
authors: Chou
authors: Daniel
authors: D
authors: Lundell
authors: Chung-Her
authors: CH
authors: Jenh
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005232:Fatty Acids, Volatile / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000893:Anti-Inflammatory Agents; D018925:Chemokines; D016207:Cytokines; D005230:Fatty Acids, Nonesterified; D005232:Fatty Acids, Volatile; D008070:Lipopolysaccharides; D016753:Interleukin-10; D015232:Dinoprostone; D002118:Calcium