CD200R1 agonist attenuates LPS-induced inflammatory response in human renal proximal tubular epithelial cells by regulating TLR4-MyD88-TAK1-mediated NF-κB and MAPK pathway
CD200R1 agonist attenuates LPS-induced inflammatory response in human renal proximal tubular epithelial cells by regulating TLR4-MyD88-TAK1-mediated NF-κB and MAPK pathway
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DOI：
10.1016/j.bbrc.2015.03.026
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发表时间：
2015-05-01
影响因子：
3.1
通讯作者：
Yi, Zhuwen
中科院分区：
文献类型：
--
作者：
Ding, Yan;Yang, Huilan;Yi, Zhuwen
先前的研究已经揭示了CD200Fc （CD200R1的激动剂）在自身免疫性疾病中的抗炎作用。然而，它对肾脏疾病的抗炎作用知之甚少。本研究的目的是评估CD200Fc在调节脂多糖（LPS）诱导的人肾近端小管上皮细胞（hRPTECs）炎症反应中的功能及其可能的机制。LPS降低了hrptec中CD200R1的表达，CD200Fc以剂量依赖的方式减弱了这种作用。此外，CD200Fc抑制lps诱导的TLR4及其适配分子（MyD88和TAK1的磷酸化）的表达，并在hRPTECs细胞中消除其与MyD88或TAK1的相互作用。CD200Fc还减弱了lps诱导的I κ B磷酸化、nf - κ B- p65向核转运，并增加了hrptec中ERK1/2、p38和JNK的磷酸化。此外，CD200Fc抑制lps诱导的促炎介质在hRPTECs中的释放，包括IL-1 β、IL-6、IL-8、MCP-1、VCAM-1、ICAM-1、tnf - α、inf - α和inf - γ。我们的研究结果表明，CD200Fc可以抑制lps诱导的hrptec中tlr4介导的炎症反应，从而可能有益于狼疮性肾炎等肾脏疾病的治疗。(C) 2015爱思唯尔公司版权所有。
Previous studies have revealed the anti-inflammatory effect of CD200Fc, an agonist of CD200R1 in autoimmune disease. However, little is known about its anti-inflammatory effects in kidney diseases. The aim of this study is to assess the function of CD200Fc in regulating lipopolysaccharide (LPS)-induced inflammatory response in human renal proximal tubular epithelial cells (hRPTECs) and the possible mechanisms. LPS reduced the CD200R1 expression in hRPTECs, and this effect was attenuated by CD200Fc in a dose-dependent manner. In addition, CD200Fc inhibited LPS-induced expressions of TLR4 and its adapter molecule (MyD88 and phosphorylation of TAK1), and abolished its interactions with MyD88 or TAK1 in hRPTECs cells. CD200Fc also attenuated LPS-induced phosphorylation of I kappa B, NF-kappa B-P65 translocation to nucleus, and increased phosphorylation of ERK1/2, p38 and JNK in hRPTECs. Moreover, CD200Fc suppressed the LPS-induced release of pro-inflammatory mediators in hRPTECs, including IL-1 beta, IL-6, IL-8, MCP-1, VCAM-1, ICAM-1, TNF-alpha, INF-alpha and INF-gamma. Our results suggested that CD200Fc could inhibit the TLR4-mediated inflammatory response in LPS-induced hRPTECs, thus might be beneficial for the treatment of renal disease, such as lupus nephritis. (C) 2015 Elsevier Inc. All rights reserved.