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.