title: 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.
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.
authors: Department of Dermatology, Maternal and Child Health Care Hospital of Hainan Province, Haikou 570206, China; Department of Cardiology, Hainan General Hospital, Haikou 570102, China.
authors: Yan
authors: Y
authors: Ding
authors: Department of Dermatology, General Hospital of Guangzhou Military Command of PLA, Southern Medical University, Guangzhou 510010, China. Electronic address: yanghuilangz@163.com.
authors: Huilan
authors: H
authors: Yang
authors: Department of Dermatology, Maternal and Child Health Care Hospital of Hainan Province, Haikou 570206, China. Electronic address: xiangweihn2@163.com.
authors: Wei
authors: W
authors: Xiang
authors: Department of Nephropathy, Children's Medical Center, The Second Xiangya Hospital, Central South University, Changsha 410000, China.
authors: Xiaojie
authors: X
authors: He
authors: Department of Cardiology, Hainan General Hospital, Haikou 570102, China.
authors: Wang
authors: W
authors: Liao
authors: Department of Nephropathy, Children's Medical Center, The Second Xiangya Hospital, Central South University, Changsha 410000, China.
authors: Zhuwen
authors: Z
authors: Yi
mesh_terms: D000954:Antigens, Surface; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D064446:Orexin Receptors; D011956:Receptors, Cell Surface / Q000819:agonists*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D000954:Antigens, Surface; D008070:Lipopolysaccharides; D020930:MAP Kinase Kinase Kinases; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D064446:Orexin Receptors; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D000099151:MAP Kinase Kinase Kinase 7; C477337:CD200R1 protein, human; C507779:MYD88 protein, human; C495345:TLR4 protein, human
keywords: CD200Fc; Human renal proximal tubular epithelial cells; Inflammation; MAPK; NF-κB; TLR4