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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

ZHAO Li-Qin, HUANG Jie-Li, YU Ying, Lu Ying, FU Lan-Jun, WANG Jun-Ling, WANG Yan-Dao, YU Chen

Division of Nephrology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China； Department of Nephrology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China

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.

Key words: toll-like receptor 4; lipopolysaccharide; angiotensin II type 1 receptor blockers; NF-kappa B; inflammation

Received: 2013-04-23　　Accepted: 2013-06-20

Corresponding author: 余晨　　E-mail: yuchen2001@hotmail.com

Citing This Article：

ZHAO Li-Qin, HUANG Jie-Li, YU Ying, Lu Ying, FU Lan-Jun, WANG Jun-Ling, WANG Yan-Dao, YU Chen. 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. Acta Physiol Sin 2013; 65 (6): 623-630 (in Chinese with English abstract).