Dexamethasone Inhibits IL-33Production From Human Airway Smooth Muscle Cells Induced By LPS And TNF-α

Objective:IL-33(also called IL-1F11, IL-1family11th member) is the latest defined member of the IL-1cytokine family. It is a tissue derived cytokine which locates in cell nucleus by binding to chromatin rather than in cytoplasm. IL-33promotes Th2cytokine production by binding to its receptor ST2, causes disturbance of Th2/Thl immune response and plays a very important role in asthma pathogenesis. Lipopolysaccharide (LPS), a component of Gram negative bacterial cell wall, act as a potent initiator of inflammatory in asthma via toll like receptor4(TLR4). TLR-4is demonstrated to express in cultured ASMCs (airway smooth muscle cells) and can combine LPS to mediate inflammatory response. We hypothesized LPS-stimulated ASMCs produced IL-33. We also hypothesized that LPS and TNF-α, a cytokine found in steroid-dependent asthma have a synergistic ability to up-regulate IL-33expression and the glucocorticosteroids Dexamethasone inhibited all processes.Methods:We obtained HASMC from main bronchial segments (0.5-1.0cm diameter) of subjects undergoing surgery in Tongji Hospital. Experiments were performed with cells from passage6to passage8. Cells were seeded at a density of105/cm2and stimulated by LPS, TNF-α, atopic asthmatic serum and IgE separately or combinedly. And we added DXM, inhibitors of p38MAPK and ERK (SB203580and PD98059) into cell culture medium30min prior to the stimulators. HASMC supernatants were collected at various time point for ELISA and cells were collected for RNA extraction and then for real-time quantitative PCR.Results:LPS induced up-regulation of IL-33mRNA in HASMC in a time-depended manner. Dexamethasone inhibited IL-33production from HASMC induced by LPS and TNF-α (p<0.05). SB203580and PD98059partly inhibited IL-33induction by LPS and TNF-α IL-33proteins in cell supernatants detected by ELISA showed stable at-20pg/ml.Conclusion:Glucocorticosteroids play major role in anti-inflammation by inhibiting various chemokines and cytokines production. The present study demonstrated that DXM inhibited IL-33production induced by LPS and TNF-α, while partly inhibition was conducted by inhibitors of p38and ERK. At present Glucocorticosteroids remain the cornerstone of asthma control and treatment.