CD200R1激动剂通过调节TLR4-MyD88-TAK1介导的NF-κB和MAPK通路减轻脂多糖诱导的人肾近端小管上皮细胞炎症反应。

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.

作者信息

Ding Yan, Yang Huilan, Xiang Wei, He Xiaojie, Liao Wang, Yi Zhuwen

机构信息

Department of Dermatology, Maternal and Child Health Care Hospital of Hainan Province, Haikou 570206, China; Department of Cardiology, Hainan General Hospital, Haikou 570102, China.

Department of Dermatology, General Hospital of Guangzhou Military Command of PLA, Southern Medical University, Guangzhou 510010, China.

出版信息

Biochem Biophys Res Commun. 2015 May 1;460(2):287-94. doi: 10.1016/j.bbrc.2015.03.026. Epub 2015 Mar 17.

DOI:10.1016/j.bbrc.2015.03.026

Abstract

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 IκB, NF-κB-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-1β, IL-6, IL-8, MCP-1, VCAM-1, ICAM-1, TNF-α, INF-α and INF-γ. 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.

摘要

先前的研究已经揭示了CD200Fc（一种CD200R1激动剂）在自身免疫性疾病中的抗炎作用。然而，关于其在肾脏疾病中的抗炎作用知之甚少。本研究的目的是评估CD200Fc在调节人肾近端小管上皮细胞（hRPTECs）中脂多糖（LPS）诱导的炎症反应中的功能及其可能的机制。LPS降低了hRPTECs中CD200R1的表达，而CD200Fc以剂量依赖性方式减弱了这种作用。此外，CD200Fc抑制了LPS诱导的TLR4及其衔接分子（MyD88和TAK1的磷酸化）的表达，并消除了其在hRPTECs细胞中与MyD88或TAK1的相互作用。CD200Fc还减弱了LPS诱导的hRPTECs中IκB的磷酸化、NF-κB-P65向细胞核的易位，并增加了ERK1/2、p38和JNK的磷酸化。此外，CD200Fc抑制了LPS诱导的hRPTECs中促炎介质的释放，包括IL-1β、IL-6、IL-8、MCP-1、VCAM-1、ICAM-1、TNF-α、INF-α和INF-γ。我们的结果表明，CD200Fc可以抑制LPS诱导的hRPTECs中TLR4介导的炎症反应，因此可能对治疗肾脏疾病（如狼疮性肾炎）有益。