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).
Conclusion: The IL-33/ST2 pathway may promote airway remodeling in asthma through activating HLF-1 to over-express FN1 and Col1.