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.
- Author:
Li-Qin ZHAO
1
;
Jie-Li HUANG
;
Ying YU
;
Ying LU
;
Lan-Jun FU
;
Jun-Ling WANG
;
Yan-Dao WANG
;
Chen YU
Author Information
1. Division of Nephrology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China; Central Laboratory, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. yuchen2001@hotmail.com.
- Publication Type:Journal Article
- MeSH:
Angiotensin II Type 1 Receptor Blockers;
pharmacology;
Benzimidazoles;
pharmacology;
Cells, Cultured;
Epithelial Cells;
drug effects;
metabolism;
Gene Expression Regulation;
Humans;
Kidney Tubules;
cytology;
Lipopolysaccharides;
NF-kappa B;
metabolism;
RNA, Messenger;
Receptor, Angiotensin, Type 1;
metabolism;
Signal Transduction;
Tetrazoles;
pharmacology;
Toll-Like Receptor 4;
metabolism;
Up-Regulation
- From:
Acta Physiologica Sinica
2013;65(6):623-630
- CountryChina
- Language:English
-
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.
