C1q/TNF-related protein-3 (CTRP-3) attenuates lipopolysaccharide (LPS)-induced systemic inflammation and adipose tissue Erk-1/-2 phosphorylation in mice in vivo
C1q/TNF-related protein-3 (CTRP-3) attenuates lipopolysaccharide (LPS)-induced systemic inflammation and adipose tissue Erk-1/-2 phosphorylation in mice in vivo
复制标题
DOI：
10.1016/j.bbrc.2014.06.054
复制
发表时间：
2014-09-12
影响因子：
3.1
通讯作者：
Schaeffler, Andreas
中科院分区：
文献类型：
--
作者：
Schmid, Andreas;Kopp, Andrea;Schaeffler, Andreas
背景：C1 q/TNF相关蛋白是脂联素旁系同源蛋白家族的一个成员。CTRP-3代表了一种在脂肪组织中强表达的新型脂肪因子，并显示出在体外抑制脂肪细胞和单核细胞中的趋化因子和细胞因子释放。研究的目的是获得CTRP-3是体内有效的抗炎脂肪因子的原理证明。与细菌脂多糖（LPS）作用2 h。用CTRP-3 i. p.或静脉内（i. v.）通过实时RT-PCR、ELISA和Western印迹分析来分析LPS（1 μ g i. p.）显著增加小鼠血清IL-6和MIP-2水平以及附睾脂肪组织中IL-6和MIP-2的表达，而CTRP-3（10 μ g i. p.）单独或PBS（i. p.）没有效果。在LPS应用之前通过CTRP-3腹膜内预处理小鼠显著减弱LPS诱导的细胞因子水平，但对脂肪组织细胞因子mRNA表达没有影响。与腹膜内施用CTRP-3相反，全身静脉内施用不足以抑制LPS诱导的细胞因子水平或mRNA组织表达。CTRP-3腹腔注射显著减弱了LPS诱导的腹股沟脂肪组织中Erk-1/-2的磷酸化。结论：本研究证明了新的脂肪因子CTRP-3是体内LPS诱导的全身炎症和LPS诱导的脂肪组织信号传导的有效抑制剂。(C)由Elsevier Inc.出版。
Background: The C1q/TNF-related proteins comprise a growing family of adiponectin paralogous proteins. CTRP-3 represents a novel adipokine with strong expression in adipose tissue and was shown to inhibit chemokine and cytokine release in adipocytes and monocytes in vitro. The aim of the study was to gain the proof of principle that CTRP-3 is a potent anti-inflammatory adipokine in vivo.Methods: C57BL/6N mice were treated intraperitoneally (i.p.) with bacterial lipopolysaccharide (LPS) for 2 h. The effects of a 30 min pre-treatment with CTRP-3 i.p. or intravenously (i.v.) on systemic and on epididymal, perirenal and subcutaneous adipose tissue inflammation was analyzed via real-time RT-PCR, ELISA and Western blot analysis.Results: LPS (1 mu g i.p.) significantly increased serum IL-6 and MIP-2 levels as well as epididymal adipose tissue expression of IL-6 and MIP-2 in mice, whereas CTRP-3 (10 mu g i.p.) alone or PBS (i.p.) had no effect. Pre-treatment of mice by CTRP-3 i.p. prior to LPS application significantly attenuated LPS-induced cytokine levels but had no effect on adipose tissue cytokine mRNA expression. In contrast to i.p. application of CTRP-3, systemic i.v. application was not sufficient to inhibit LPS-induced cytokine levels or mRNA tissue expression. CTRP-3 given i.p. significantly attenuated LPS-induced phosphorylation of Erk-1/-2 in inguinal adipose tissue.Conclusion: The present study shows the proof of principle that the novel adipokine CTRP-3 is a potent inhibitor of LPS-induced systemic inflammation and LPS-induced signaling in adipose tissue in vivo. (C) 2014 Published by Elsevier Inc.