ABSTRACT
Objective:To investigate YKL-40-mediated inflammation in human bronchial epithelial cells and analyzed the soluble factors secreted by bronchial epithelial cells exposed to YKL-40 that were responsible for increasing proliferation and migration of primary normal human bronchial smooth muscle cells (BSMCs).Methods:YKL-40-induced inflammation was assayed in two human bronchial epithelial cells (BEAS-2B cell line and primary human bronchial epithelial cells ,namely HBECs).In addition,we treated BEAS-2B cells and HBECs with YKL-40,and added the conditioned culture media ( YKL-40-BEAS-2B-CM) and ( YKL-40-HBECs-CM) to BSMCs.The proliferation and migration of BSMCs were determined by premixed WST-1 cell proliferation reagent and QCM chemotaxis migration assay ,respectively.Results: Bronchial epithelial cells treated with YKL-40 resulted in a significant increase of IL-8 production,but have no effect about RANTES ,Eotaxin and TNF-α.YKL-40-BEAS-2B-CM and YKL-40-HBECs-CM induced IL-8 was found to further stimulate proliferation and migration of BSMCs ,and the effects were inhibited after neutralizing IL-8.Conclusion:Through investigating the interaction of airway epithelium and smooth muscle ,our findings implicate that YKL-40 may be involved in the inflammation of asthma by induction of IL-8 from epithelium,subsequently contributing to BSMCs proliferation and migration.Moreover, inhibition of IL-8 signaling is a potential therapeutic target for YKL-40-induced inflammation and remodeling of asthma.
ABSTRACT
PURPOSE: Human bronchial smooth muscle cell(HBSMC) plays an important role in the remodeling of the airways in asthma. Vascular endothelial growth factor(VEGF) is a multifunctional cytokine, which induces edema, angiogenesis, vascular remodeling, mucus metaplasia, subepithelial fibrosis, and antigen-induced Th2 inflammation. Transforming growth factor-beta(TGF-beta) is a growth modulator of HBSMC and an important cytokine in airway remodeling. We investigated the effect of dexamethasone on the release of VEGF from HBSMC stimulated with platelet-derived growth factor(PDGF) and TGF-beta. METHODS: HBSMC cultured in 10 percent FCS-DMEM media was growth-arrested in serum-deprived medium for 48 hours. Dexamethasone and TGF-beta were added and incubated for 16 hours before stimulation with PDGF. After 24 hours of stimulation, culture medium was harvested and stored at -80 degrees C until ELISA for VEGF was performed. RESULTS: The release of VEGF was significantly increased after stimulation with PDGF (P<0.01). The production of VEGF pretreated with TGF-beta before stimulation with PDGF was higher than those without TGF-beta pretreatment(P<0.01). Dexamethasone suppressed the release of VEGF in HBSMC stimulated with PDGF(P<0.01), TGF-beta and PDGF(P<0.01). CONCLUSION: PDGF and TGF-beta may be one of the key mediators in inducing airway remodeling and glucocorticoid, and can be used as useful therapies to prevent airway vascular remodeling by modulating the VEGF on airway smooth muscle cells.