Abstract
Abstract Rationale: Asthma is a chronic lung disease characterized by inflammation of bronchial epithelium. House dust mite (HDM) is a common allergen that triggers asthma. IκBζ is a newly recognized member of the NFκB family that is induced in lung epithelial cells to regulate their production of cytokines. We hence analyzed how IκBζ might modulate HDM‘s induction of IL-6 and GMCSF in lung epithelial cells. Methods: We co-cultured primary human bronchial epithelial cells or BEAS2B cells with HDM alone or with HDM-treated human monocytes, macrophages or dendritic cells and measured GMCSF, IL-6 and IκBζ protein expression. Results: Bronchial epithelial cells expressed IκBζ and released IL-6 and GMCSF only when co-cultured with HDM treated monocytes. However, these epithelial cells did not respond to direct HDM stimulation when cultured alone or to co-culture with HDM-treated macrophages or dendritic cells. The monocyte co-culture response correlated with its IL-1β release and was blocked by IL-1 receptor antagonist and the TLR4 antagonist Rhodobacter sphaeroides LPS. GFP tagged IκBζ accumulated in the nucleus of epithelial cells and si-IκBζ suppressed the epithelial release of IL-6 and GMCSF. Conclusions: Monocytes release IL-1β in response to HDM thus inducing the lung epithelial cell IκBζ-mediated expression of asthma associated inflammatory cytokines. We propose that control of IκBζ expression deserves future study as a key regulator of HDM induced asthma.
Published Version
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