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
in English
| WPRIM (Western Pacific)
| ID: wpr-297529
Responsible library:
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.
Full text:
Available
Database:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
Tetrazoles
/
Benzimidazoles
/
RNA, Messenger
/
Signal Transduction
/
Up-Regulation
/
Cells, Cultured
/
Gene Expression Regulation
/
Lipopolysaccharides
/
NF-kappa B
Limits:
Humans
Language:
English
Journal:
Acta Physiologica Sinica
Year:
2013
Document type:
Article