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.
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.
Authors: Levi D Maston; David T Jones; Wieslawa Giermakowska; Tamara A Howard; Judy L Cannon; Wei Wang; Yongyi Wei; Weimin Xuan; Thomas C Resta; Laura V Gonzalez Bosc Journal: Am J Physiol Lung Cell Mol Physiol Date: 2017-02-17 Impact factor: 5.464
Authors: Moeed Akbar; Lindsay A N Crowe; Michael McLean; Emma Garcia-Melchor; Lucy MacDonald; Kristyn Carter; Umberto G Fazzi; David Martin; Angus Arthur; James H Reilly; Iain B McInnes; Neal L Millar Journal: Proc Natl Acad Sci U S A Date: 2021-09-28 Impact factor: 11.205