Candesartan inhibits LPS-induced expression increase of toll-like receptor 4 and downstream inflammatory factors likely via angiotensin II type 1 receptor independent pathway in human renal tubular epithelial cells / 生理学报
Acta Physiologica Sinica
; (6): 623-630, 2013.
Article
em En
| WPRIM
| ID: wpr-297529
Biblioteca responsável:
WPRO
ABSTRACT
The present study was to determine whether candesartan, an angiotensin II type 1 receptor blocker (ARB), exerts anti-inflammatory effects through inhibiting the toll-like receptor 4 (TLR4) pathway in human renal tubular epithelial cells (HKCs). The experiments were carried on cultured HKCs. By means of flow cytometry, Western blot, RT-PCR and ELISA techniques, the TLR4 protein, angiotensin II type 1 receptor (AT1R) and phosphorylated nuclear factor-kappa B (NF-κB) p65 protein level, mRNA levels of macrophage chemoattractant protein-1 (MCP-1) and regulated upon expression normal T cell expressed and secreted (RANTES), as well as MCP-1 and RANTES protein concentrations in conditioned media were measured. The results showed that lipopolysaccharide (LPS) upregulated the TLR4 protein level in cultured HKCs. Application of LPS increased NF-κB activation and induced release of its downstream inflammatory factors including MCP-1 and RANTES. Candesartan reversed LPS-induced upregulation of TLR4 expression, inhibited NF-κB activation, and reduced MCP-1 and RANTES release. However, knockdown on AT1R by siRNA did not change those previous effects of candesartan. These results suggest that candesartan-induced anti-inflammatory effect may be through a novel pathway, independent of AT1R.
Texto completo:
1
Base de dados:
WPRIM
Assunto principal:
Farmacologia
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Tetrazóis
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Benzimidazóis
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RNA Mensageiro
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Transdução de Sinais
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Regulação para Cima
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Células Cultivadas
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Regulação da Expressão Gênica
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Lipopolissacarídeos
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NF-kappa B
Limite:
Humans
Idioma:
En
Revista:
Acta Physiologica Sinica
Ano de publicação:
2013
Tipo de documento:
Article