Resveratrol inhibits rat pulmonary fibroblast proliferation through modulation of TLR4/NF-B pathway

Abstract

Resveratrol shows a powerful therapeutic effect in several cardiovascular diseases and cancer. Recent studies suggest a protective role of resveratrol in pulmonary fibrosis, but the underlying mechanism remains unknown. The aim of the present study is to investigate the anti-inflammatory effect of resveratrol on pulmonary fibrosis and reveal the role of toll like receptor 4 (TLR4) signaling pathway during the process. Pulmonary fibrosis (PF) model in rats was induced by endotracheal perfusion of bleomycin (BLM). Resveratrol treatment was given for three weeks. Blood samples and lung tissues were collected for further investigation. Results showed that the level of interleukin(IL)-1 and IL-6 in blood and lung tissue were both elevated in PF rats when compared with control rats (P<0.05). Resveratrol treatment significantly decreased IL-1 and IL-6 level (P<0.05). Real-time polymerase chain reaction (PCR) and western blot both showed that TLR4 expression in lung tissue from PF rats was upregulated while resveratrol treatment significantly decreased TLR4 expression (P<0.05). Furthermore, primary rat pulmonary fibroblast was cultured. Lipopolysaccharide (LPS) induced cellular proliferation and increased TLR4 and NF-κB expression while NF-κB inhibitor BAY 11-7085 abolished the cell proliferation induced by LPS. Increased TLR4 and NF-κB expression induced by LPS incubation were both diminished by resveratrol (P<0.05). Cellular proliferation was also inhibited by resveratrol treatment. In conclusion, the anti-inflammatory effect of resveratrol may contribute its role in antiproliferation of pulmonary fibroblast and PF therapy. TLR4/NF-κB signaling pathway is also involved in the process.