Toll-Like Receptor 4 Signaling is Involved in IgA-Stimulated Mesangial Cell Activation
Yonsei Medical Journal
;
: 610-615, 2011.
Artigo
em Inglês
| WPRIM
| ID: wpr-33259
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 ANDMETHODS:
Mouse mesangial cells were stimulated with lipopolysaccharide (LPS) (1 microg/mL), IgA (20 microg/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), Ikappa-Balpha 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 Ikappa-Balpha 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 Ikappa-Balpha 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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Fosforilação
/
RNA Mensageiro
/
Ensaio de Imunoadsorção Enzimática
/
Camundongos Transgênicos
/
Transdução de Sinais
/
Fibronectinas
/
Quimiocina CCL2
/
Proteínas I-kappa B
/
Interferência de RNA
/
MAP Quinases Reguladas por Sinal Extracelular
Limite:
Animais
Idioma:
Inglês
Revista:
Yonsei Medical Journal
Ano de publicação:
2011
Tipo de documento:
Artigo
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