Résumé
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.
Sujets)
Humains , Antagonistes du récepteur de type 1 de l'angiotensine-II , Pharmacologie , Benzimidazoles , Pharmacologie , Cellules cultivées , Cellules épithéliales , Métabolisme , Régulation de l'expression des gènes , Tubules rénaux , Biologie cellulaire , Lipopolysaccharides , Facteur de transcription NF-kappa B , Métabolisme , ARN messager , Récepteur de type 1 à l'angiotensine-II , Métabolisme , Transduction du signal , Tétrazoles , Pharmacologie , Récepteur de type Toll-4 , Métabolisme , Régulation positiveRésumé
Peroxisome proliferator-activated receptor (PPAR), a member of nuclear hormone receptor superfamily, has 3 subtypes, namely, PPARα, PPARβ/δ, and PPARγ; among them PPARγ plays an important role in adipogenesis, lipid metabolism, insulin sensitivity, inflammation, atherosclerosis, and blood pressure controlling. This article reviews the relationship between PPARγ and diabetec nephropathy.
Résumé
The effect of 1-deoxynojirimycin(DNJ)on the proliferation of rat mesangial cells was observed and its mechanism was explored.The results showed that DNJ significantly inhibited the proliferation of rat mesangial cells induced by high glucose in time-and dose-dependent manners.DNJ significantly decreased expressions of?-smooth muscle action(?-SMA),integrin?1 mRNA and protein and focal adhesion kinase (FAK)protein stimulated by high glucose in rat mesangial cells(P