siRNA-Act1 inhibits the function of IL-17 on lung fibroblasts via the NF-κB pathway.

BACKGROUND Interleukin (IL)-17-producing T lymphocytes play a role in pulmonary fibrosis, but the possible mechanism of IL-17 on lung fibroblasts remains uncertain. OBJECTIVES To explore the role and possible mechanism of IL-17 on lung fibroblasts. METHODS A mouse model of pulmonary fibrosis was established by intratracheal administration of 5 mg/kg bleomycin. At 14 days following bleomycin administration the pulmonary fibroblasts were isolated, cultured and identified. siRNA for activator 1 (Act1) were transfected into lung fibroblasts, which were cocultured with IL-17. The NF-κB pathway was detected for IL-17 on the lung fibroblasts. RESULTS IL-17R was increased significantly at 14 days in the bleomycin-induced pulmonary fibroblast model, exogenous IL-17 significantly promoted the proliferation of the pulmonary fibroblasts in primary culture and obviously increased the expression of α-smooth muscle actin and type I and type III collagen in the fibroblasts. We found that IL-17 rapidly activated the NF-κB signaling pathway through activated phosphorylated p65 and IκB, and all roles of IL-17 on lung fibroblasts were inhibited under the interference for the expression of Act1 in lung fibroblasts. CONCLUSION IL-17 may directly promote the proliferation, transformation and collagen synthesis of lung fibroblasts via the NF-kB signaling pathway, which can be inhibited by the interference for the expression of Act1.