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D-Dopachrome tautomerase promotes IL-6 expression and inhibits adipogenesis in preadipocytes

机译:D-Dopachrome互变异构酶促进前脂肪细胞中IL-6的表达并抑制脂肪生成

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We previously identified d-dopachrome tautomerase (DDT) as a novel adipokine whose mRNA levels in adipocytes are negatively correlated with obesity-related clinical parameters, and which acts on adipocytes to regulate lipid metabolism. Here we investigated functions of DDT on preadipocytes. Recombinant DDT (rDDT) enhanced both the expression and secretion of interleukin-6 (IL-6) in SGBS cells, a human preadipocyte cell line. Treatment with rDDT increased levels of phosphorylated ERK1/2, but not p38, in SGBS cells, and rDDT-induced IL-6 mRNA expression was attenuated by pretreatment with an ERK inhibitor, U0126. Knockdown of CD74, but not CD44, inhibited rDDT-induced IL-6 mRNA expression in SGBS cells. These results suggested that the rDDT-induced IL-6 expression in preadipocytes occurred through the CD74-ERK pathway. Furthermore, in SGBS cells subjected to adipogenic induction, rDDT decreased the amount of triacylglycerol, number of cells with oil droplets, and levels of mRNA encoding adipocyte marker proteins. Increased expression of CCAAT/enhancer binding protein families and peroxisome proliferator-activated receptor γ2 during adipogenesis was inhibited in the cells treated with rDDT. These results suggested DDT to inhibit adipogenesis by suppressing the expression of genes encoding adipogenic regulators in preadipocytes.
机译:我们先前确定d-多巴色素互变异构酶(DDT)为新型脂肪因子,其脂肪细胞中的mRNA水平与肥胖相关的临床参数呈负相关,并且作用于脂肪细胞以调节脂质代谢。在这里,我们研究了滴滴涕对前脂肪细胞的功能。重组DDT(rDDT)增强了人脂肪细胞前体SGBS细胞中白介素6(IL-6)的表达和分泌。用rDDT处理可增加SGBS细胞中磷酸化的ERK1 / 2的水平,但不会增加p38的水平,并且通过ERK抑制剂U0126的预处理减弱了rDDT诱导的IL-6 mRNA表达。击倒CD74而不是CD44可以抑制SGBS细胞中rDDT诱导的IL-6 mRNA表达。这些结果表明,rDDT诱导的前脂肪细胞中IL-6表达是通过CD74-ERK途径发生的。此外,在经历脂肪诱导的SGBS细胞中,rDDT降低了三酰甘油的量,具有油滴的细胞数量以及编码脂肪细胞标记蛋白的mRNA水平。在用rDDT处理的细胞中,脂肪形成期间CCAAT /增强子结合蛋白家族和过氧化物酶体增殖物激活的受体γ2的表达增加受到抑制。这些结果表明,滴滴涕通过抑制前脂肪细胞中编码脂肪形成调节剂的基因的表达来抑制脂肪形成。

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