House Dust Mite Allergens and the Induction of Monocyte Interleukin 1β Production That Triggers an IκBζ-Dependent Granulocyte Macrophage Colony-Stimulating Factor Release from Human Lung Epithelial Cells

Asthma is a chronic lung disease characterized by inflammation centered upon bronchial epithelium. House dust mite is one of the most common respiratory allergens that trigger exacerbations of asthma. IκBζ (gene NFKBIZ) is a recently recognized member of the NF-κB family that can be induced in mononuclear phagocytes and lung epithelial cells and has been shown to play a prominent role in epithelial cell function. We therefore analyzed the role of IκBζ in regulating lung epithelial cell cytokine responses to house dust mite mix (HDM). We found that human bronchial epithelial cells express IκBζ and release IL-6 and granulocyte macrophage colony-stimulating factor (GMCSF) when cocultured with human monocytes and HDM. This response is blocked in the presence of IL-1 receptor antagonist (IL-1Ra), indicating that it is IL-1 mediated. Neither HDM-stimulated macrophages nor dendritic cells release IL-1β and subsequently induce cytokine release from the bronchial epithelial cells. Rhodobacter sphaeroides LPS (RS-L...