短链脂肪酸对脂多糖的抗炎作用,或通过激活内皮细胞肿瘤坏死因子alpha-Stimulated GPR41/43 hdac抑制。

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李米,货车每BCAM甘伟鸿洋纺,Folkerts G, Garssen J

短链脂肪酸对脂多糖的抗炎作用,或通过激活内皮细胞肿瘤坏死因子alpha-Stimulated GPR41/43 hdac抑制。

杂志。2018年5月23日,9:533。doi: 10.3389 / fphar.2018.00533。eCollection 2018。

PubMed ID

29875665 (在PubMed

]

文摘

背景和目的:在此之前,我们发现短链脂肪酸(SCFA)抑制LPS或TNFalpha-induced内皮炎症反应和过度血管细胞粘附molecule-1 (VCAM-1)表达式,动脉粥样硬化发展的两个重要步骤。然而,所涉及的机制仍不清楚。我们假设的影响SCFA与受体激活g蛋白耦合的41/43 (GPR41/43)和/或抑制组蛋白去乙酰酶抑制剂(hdac)。方法:GPR41/43的表达式和位置和HDAC3人类脐静脉内皮细胞(HUVEC)被证实。HUVEC pre-incubated有乙酸、丁酸盐或丙酸单独或结合GLPG0974 (GPR43 GLPG,对手)或beta-hydroxybutyrate (SHB,拮抗剂GPR41)然后暴露于有限合伙人或TNFalpha。白介素(IL) 6和引发水平和VCAM-1表达测定。与丁酸HDAC活性测定治疗后,丙酸和trichostatin (TSA, HDAC抑制剂)。外周血单核细胞(PBMC)的水平也决定TSA治疗后的粘合剂。结果:GPR41/43表示HUVEC的膜和HDAC3位于细胞质和细胞核。GLPG和/或SHB治疗恢复了抑制醋酸对il - 6的影响和引发生产丙酸和丁酸的抑制作用或对il - 6生产,而不是引发。 In contrast, GLPG and/or SHB treatments did not affect the inhibitory effects of butyrate or propionate on TNFalpha-induced VCAM-1 expression. TSA showed similar effects on IL-8 production and VCAM-1 expression as butyrate and propionate. In addition, TSA significantly inhibited the adhesion of PBMC to an endothelial monolayer. Conclusion: Activation of GPR41/43 mediates the effects of acetate on IL-6 and IL-8 production and the effects of butyrate and propionate on IL-6 production. Furthermore, inhibition of HDACs mediates the effects of butyrate and propionate on IL-8 production, VCAM-1 expression, and PBMC adhesion to an endothelial monolayer. These data indicate the beneficial roles of SCFA in preventing vascular inflammation and relevant diseases by activation of GPR41/43 and inhibition of HDACs.

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药物靶点

药物	目标	类	生物	药理作用	行动
glpg - 0974	游离脂肪酸受体2	蛋白质	人类	未知的	拮抗剂	细节