AIM:To investigate the effect of short-chain fatty ac-ids (SCFAs) on production of prostaglandin E2 (PGE2),cytokines and chemokines in human monocytes.METHODS:Human neutrophils and monocytes were isolated from human w...AIM:To investigate the effect of short-chain fatty ac-ids (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 Enrich-ment 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 ofSCFAs 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 in-duce human monocyte release of PGE2 and that this effect can be enhanced in the presence of lipopolysac-charide (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 specifi cally 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.展开更多
文摘AIM:To investigate the effect of short-chain fatty ac-ids (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 Enrich-ment 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 ofSCFAs 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 in-duce human monocyte release of PGE2 and that this effect can be enhanced in the presence of lipopolysac-charide (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 specifi cally 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.
