title: siRNA-Act1 inhibits the function of IL-17 on lung fibroblasts via the NF-κB pathway.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Respiratory Department, The 2nd Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Zhaoxing
authors.initials: Z
authors.lastname: Dong
authors.forename: Yanni
authors.initials: Y
authors.lastname: Yang
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Yongxia
authors.initials: Y
authors.lastname: Li
authors.forename: Qinxin
authors.initials: Q
authors.lastname: Kang
authors.forename: Wen
authors.initials: W
authors.lastname: Lei
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Niu
authors.forename: Dianhua
authors.initials: D
authors.lastname: Wang
authors.forename: Wenlin
authors.initials: W
authors.lastname: Tai
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D054338:Cell Transdifferentiation; D003094:Collagen / Q000096:biosynthesis*; D005347:Fibroblasts / Q000378:metabolism*; D020868:Gene Silencing; D020381:Interleukin-17 / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051818:Replication Protein C / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
chemical_list: D020381:Interleukin-17; D016328:NF-kappa B; D034741:RNA, Small Interfering; D003094:Collagen; D051818:Replication Protein C