title: [IL-33/ST2 promotes airway remodeling in asthma by activating the expression of fibronectin 1 and type 1 collagen in human lung fibroblasts].
abstract: OBJECTIVE
  To investigate the IL-33-induced production of fibronectin 1 (FN1) and type 1 collagen (Col1) from human lung fibroblasts (HLF-1).
  
  
  METHODS
  The study enrolled 28 patients with asthma (asthma group) and 25 healthy controls. The IL-33 in serum was measured by ELISA. Airway remodeling and the expression of IL-33 were observed by HE staining and immunohistochemistry in biopsied specimens from 8 asthma patients and 8 controls. In vitro experiments, the production of FN1 and Col1 from HLF-1 stimulated with IL-33 at different concentrations was evaluated by real-time quantitative PCR and Western blotting.
  
  
  RESULTS
  The IL-33 level in the sera of asthma patients was significantly higher than that in controls (P<0.01). Different degrees of basement membrane thickness were present in patients with asthma, and a correlation analysis showed that the level of IL-33 in serum was positively correlated with the average thickness of basement membrane in asthma patients (r=0.829, P<0.05). The immunohistochemical results showed that IL-33 was mostly derived from injured airway epithelium. In vitro experiments, the production of FN1 and Col1 from HLF-1 stimulated with IL-33 was significantly elevated in a concentration-dependent manner (P<0.05). The IL-33-induced production of FN1 and Col1 from HLF-1 was significantly suppressed by the pretreatment with fluticasone propionate and anti-ST2 antibody (P<0.05).
  
  
  CONCLUSIONS
  The IL-33/ST2 pathway may promote airway remodeling in asthma through activating HLF-1 to over-express FN1 and Col1.
authors.affiliation: Department of Pulmonary Diseases, Qilu Hospital, Shandong University, Department of Pulmonary Diseases, Jinan Military General Hospital, Jinan 250031, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Pulmonary Diseases, Qilu Hospital, Shandong University, Jinan 250031, China.
authors.forename: Jinxiang
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Pulmonary Diseases, Qilu Hospital, Shandong University, Jinan 250031, China.
authors.forename: Jiping
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Pulmonary Diseases, Qilu Hospital, Shandong University, Jinan 250031, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, Jinan 250031, China.
authors.forename: Yingjian
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Clinical Laboratory, Jinan 250031, China.
authors.forename: Liquan
authors.initials: L
authors.lastname: Bi
authors.affiliation: Department of Pulmonary Diseases, Qilu Hospital, Shandong University, Jinan 250031, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Dong
mesh_terms: D056151:Airway Remodeling; D001249:Asthma / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D015153:Blotting, Western; D002460:Cell Line; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D008168:Lung / Q000166:cytology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D024042:Collagen Type I; D005353:Fibronectins; C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D011956:Receptors, Cell Surface