The Inflammation Induced by Lipopolysaccharide can be Mitigated by Short‐chain Fatty Acid, Butyrate, through Upregulation of IL‐10 in Septic Shock
The Inflammation Induced by Lipopolysaccharide can be Mitigated by Short‐chain Fatty Acid, Butyrate, through Upregulation of IL‐10 in Septic Shock
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DOI：
10.1111/sji.12515
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发表时间：
2017-04
影响因子：
3.7
通讯作者：
Fangyan Wang;Jiaming Liu;T. Weng;K. Shen;Z. Chen;Y. Yu;Q. Huang;G. Wang;Z. Liu;Shengwei Jin
中科院分区：
文献类型：
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作者：
Fangyan Wang;Jiaming Liu;T. Weng;K. Shen;Z. Chen;Y. Yu;Q. Huang;G. Wang;Z. Liu;Shengwei Jin
具有抗炎能力的短链脂肪酸（SCFAs）由肠道细菌产生;然而，它们对急性全身炎症的影响尚不清楚。本研究旨在探讨SCFAs乙酸盐、丙酸盐和丁酸盐对感染性休克的作用及其机制。采用LPS诱导的脓毒症模型，通过观察存活率来评价SCFAs的功能。只有丁酸盐，而不是乙酸盐或丙酸盐，可以显着降低脓毒症小鼠的死亡率。在LPS给药2 h和6 h时，通过ELISA测定血浆中TNF-α、IL-6和IL-1β的水平，以评估丁酸盐预处理对过度炎症的影响。并检测脓毒症小鼠血浆中的抗炎介质TGF-β、IL-10和LXT 4，以进一步研究脓毒症小鼠的抗炎机制。此外，通过LPS刺激鼠巨噬细胞样RAW 264.7细胞以进一步证实体内发现。丁酸盐预处理导致LPS诱导的TNF-α、IL-6和IL-1β水平升高显著减弱。然而，当检测抗炎因子时，丁酸盐预处理组显示IL-10显著增加，但TGF-β或LXT 4没有显著增加。丁酸盐预处理RAW 264.7细胞可下调LPS诱导的促炎介质IL-6和IL-1β的表达，但不影响TNF-α的水平，并增加IL-10的表达（P < 0.01）。总之，SCFA丁酸盐通过上调抗炎性IL-10显著减轻了脓毒症的炎症。
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.