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

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

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.

Keywords: CD200Fc; Human renal proximal tubular epithelial cells; Inflammation; MAPK; NF-κB; TLR4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Surface
  • Cells, Cultured
  • Epithelial Cells / metabolism
  • Humans
  • Inflammation / metabolism
  • Inflammation / prevention & control*
  • Kidney Tubules, Proximal / drug effects*
  • Kidney Tubules, Proximal / enzymology
  • Kidney Tubules, Proximal / metabolism
  • Lipopolysaccharides / pharmacology*
  • MAP Kinase Kinase Kinases / metabolism
  • MAP Kinase Signaling System*
  • Myeloid Differentiation Factor 88 / metabolism
  • NF-kappa B / metabolism*
  • Orexin Receptors
  • Receptors, Cell Surface / agonists*
  • Toll-Like Receptor 4 / metabolism

Substances

  • Antigens, Surface
  • CD200R1 protein, human
  • Lipopolysaccharides
  • MYD88 protein, human
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • Orexin Receptors
  • Receptors, Cell Surface
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • MAP Kinase Kinase Kinases
  • MAP kinase kinase kinase 7