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Toll-like receptor 4 signaling is involved in IgA-stimulated mesangial cell activation

Authors
 Beom Jin Lim  ;  Dahye Lee  ;  Hyeon Joo Jeong  ;  Soon Won Hong 
Citation
 Yonsei Medical Journal, Vol.52(4) : 610-615, 2011 
Journal Title
 Yonsei Medical Journal 
ISSN
 0513-5796 
Issue Date
2011
Abstract
PURPOSE: Deposition of polymeric IgA1 in the kidney mesangium is the hallmark of IgA nephropathy, but the molecular mechanisms of IgA-mediated mesangial responses and inflammatory injuries remain poorly understood. We hypothesize that Toll-like receptor 4 (TLR4) is involved in IgA-induced mesangial cell activation. MATERIALS AND METHODS: Mouse mesangial cells were stimulated with lipopolysaccharide (LPS) (1 μg/mL), IgA (20 μg/mL), or both, and TLR4 expression was measured by real time RT-PCR and Western blot. Intracellular responses to LPS or IgA were assessed by Western blot for ERK1/2, JNK, p38 MAP kinases (MAPKs), Iκ-Bα degradation and fibronectin secretion. MCP-1 secretion was assessed by ELISA. Small interfering RNA (siRNA) of TLR4 was used to confirm that the effects were caused by TLR4 activity. RESULTS: LPS- or IgA-treatment upregulated the levels of TLR4 mRNA and protein in cultured MMC at 24 h. LPS and IgA induced rapid phosphorylation of MAPKs, but degradation of Iκ-Bα was observed only in LPS-treated MMC. LPS, but not IgA, induced increased secretion of MCP-1 and fibronectin at 24 h or 48 h. Combined LPS and IgA treatment did not cause additional increases in TLR4 mRNA and protein levels or Iκ-Bα degradation, and MCP-1 and fibronectin secretions were less than with LPS alone. LPS- or IgA-induced TLR4 protein levels and MAPK activation were inhibited by transfection with TLR4 siRNA. CONCLUSION: These results indicate that the activation of MAPKs and MCP-1 secretion are mediated by TLR4, at least in part, in IgA-treated mesangial cells. TLR4 is involved in mesangial cell injury by induction of pro-inflammatory cytokines in IgA nephropathy.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/93263
DOI
10.3349/ymj.2011.52.4.610
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실)
Yonsei Authors
임범진(Lim, Beom Jin) ; 정현주(Jeong, Hyeon Joo) ; 홍순원(Hong, Soon Won)
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