The role of Toll like receptor 4 pathway in palmitate-induced interleukin-6 expression in human aortic vascular smooth muscle cells
10.3760/cma.j.issn.1000-6699.2013.01.021
- VernacularTitle:TLR4通路在软脂酸诱导人血管平滑肌细胞IL-6基因表达中的作用
- Author:
Jinxing QUAN
;
Xiaobo GAO
;
Haijing YANG
;
Wei CHEN
;
Weihua LI
;
Yonghong LI
;
Jing LIU
- Publication Type:Journal Article
- Keywords:
Human aortic vascular smooth muscle cells;
Palmitate;
Toll like receptor 4;
Intedeukin-6
- From:
Chinese Journal of Endocrinology and Metabolism
2013;(1):75-78
- CountryChina
- Language:Chinese
-
Abstract:
The recombinant adenovirus Toll like receptor 4 (TLR4) shRNA vector (pGSadeno-TLR4) was constructed and transfected into human aortic vascular smooth muscle cells (HA-VSMC).After HA-VSMC were treated with palmitate or different signaling pathway inhibitors,the mRNA and protein levels of interleukin-6 (IL-6)and NF-κB activity were tested with real-time PCR and ELISA,respectively.The results showed that palmitate increased mRNA and protein levels of IL-6 in HA-VSMC in a dose-dependent manner.The expression of IL-6 mRNA reached peak after treatment with 400 μmol/L of palmitate for 6 h,being 10.43 fold of control (P＜0.01).Treatment with 400 pmol/L of palmitate for 24 h maximally upregulated the protein level of IL-6,which was 2.18 fold of control (P＜0.01).NF-κB inhibitor parthenolide markedly inhibited palmitate-stimulated increased in IL-6 mRNA level by 65％ and protein level by 59％ (both P＜0.01).Protein kinase C (PKC) inhibitor chlerythrine suppressed palmitateinduced IL-6 mRNA expression by 24％ and IL-6 protein level by 28％.By contrast,extracellular signal-regulated protein kinase inhibitor PD98059 and phosphatidylinositol 3-kinase inhibitor wortmannin had no effect on the induction of IL-6 by palmitate.Blockade of TLR4 with pGSadeno-TLR4 significantly suppressed palmitate-induced IL-6 mRNA expression by 72％ and IL-6 protein expression by 75％ (both P＜0.01),along with decrease of NF-κB p65 activity decreased by 62％.These results suggest that TLR4/NF-κB and PKC pathways mediate palmitate-induced IL-6 expression in HA-VSMC.
