title: The Inflammation Induced by Lipopolysaccharide can be Mitigated by Short-chain Fatty Acid, Butyrate, through Upregulation of IL-10 in Septic Shock.
abstract: Short-chain fatty acids (SCFAs) with the anti-inflammatory capacity are produced by intestinal bacteria; however, their effect on the acute systematical inflammation remains unclear. This study aimed to investigate the effects of SCFAs, acetate, propionate and butyrate, on septic shock and the underlying mechanism. The LPS-induced septic model was used to evaluate the function of SCFAs by survival rate observation. Only butyrate, but not acetate or propionate, significantly decrease the mortality of septic mice. At 2 h and 6 h of LPS administration, the levels of TNF-α, IL-6 and IL-1β in plasma were measured by ELISA to estimate the effects of butyrate pretreatment on excessive inflammation. And the anti-inflammatory mediators including TGF-β, IL-10 and LXT4 in plasma were detected for further mechanism study in septic mice. Moreover, the murine macrophage-like RAW 264.7 cells were stimulated by LPS to further confirm the finding in vivo. Pretreatment with butyrate led to significant attenuation of the LPS-induced elevation of TNF-α, IL-6 and IL-1β levels. However, when detecting the anti-inflammatory factors, a significant increase in IL-10, but not TGF-β or LXT4, was shown in butyrate-pretreated group. Pretreatment of RAW 264.7 cells with butyrate led to downregulation of LPS-induced pro-inflammatory mediators, IL-6 and IL-1β, but did not affect the level of TNF-α, and increased IL-10 (P < 0.01). In conclusion, SCFA butyrate significantly attenuated the inflammation against sepsis through upregulation of anti-inflammatory IL-10.
authors.affiliation: School of Basic Medicine Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: F
authors.initials: F
authors.lastname: Wang
authors.affiliation: School of Environmental Science and Public Health, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Basic Medicine Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: T
authors.initials: T
authors.lastname: Weng
authors.affiliation: School of Basic Medicine Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: K
authors.initials: K
authors.lastname: Shen
authors.affiliation: School of Basic Medicine Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Intensive Care Unit, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Intensive Care Unit, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Huang
authors.affiliation: School of Basic Medicine Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: G
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Intensive Care Unit, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.affiliation: School of Basic Medicine Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: S
authors.initials: S
authors.lastname: Jin
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002087:Butyrates / Q000494:pharmacology*; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000276:immunology / Q000633:toxicity; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011422:Propionates / Q000494:pharmacology*; D000067996:RAW 264.7 Cells; D012772:Shock, Septic / Q000188:drug therapy* / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000085:Acetates; D000893:Anti-Inflammatory Agents; D002087:Butyrates; C556062:IL10 protein, mouse; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011422:Propionates; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D016753:Interleukin-10