interleukin-8 and calmidazolium

House dust mites (HDM) have been shown to be important sources of indoor allergens associated with asthma and other allergic conditions. While exogenous proteases from allergens have a direct proinflammatory role in the respiratory tract, the precise mechanisms underlying the release of cytokines from the respiratory epithelium are unclear.. The present study examines that extracellular signal-regulated kinase (ERK) activated downstream of the Ca(2+)-sensitive tyrosine kinase plays an important role in the efficient activation of the HDM-induced IL-8 signaling pathway.. We examined the effect of HDM, and the role of the Ca(2+)/calmodulin system and mitogen-activated protein kinases, on IL-8 expression in human lung epithelial cells.. In H292 cells, HDM induced IL-8 release in a time- and/or dose-dependent manner. This IL-8 release was abolished by treatment with intracellular Ca(2+) chelator (BAPTA-AM), but not by EGTA or nifedipine. Calmodulin inhibitor (calmidazolium) and tyrosine kinase inhibitor (genistein) almost completely blocked IL-8 release by HDM. PD98,059, an ERK pathway inhibitor, completely abolished HDM-induced IL-8 release. Moreover, PD98,059, BAPTA-AM, calmidazolium and genistein suppressed the HDM-induced ERK phosphorylation.. HDM-induced IL-8 production is predominantly regulated by Ca(2+)/calmodulin signaling, and ERK plays an important role in signal transmission for efficient activation of the HDM-induced IL-8 signaling pathway.

Topics: Allergens; Animals; Blotting, Western; Calcium-Calmodulin-Dependent Protein Kinases; Cells, Cultured; Chelating Agents; Dermatophagoides farinae; Egtazic Acid; Enzyme Activation; Enzyme Inhibitors; Epithelial Cells; Extracellular Signal-Regulated MAP Kinases; Flavonoids; Gene Expression; Genistein; Humans; Imidazoles; Interleukin-8; Phosphorylation; Respiratory Mucosa; Reverse Transcriptase Polymerase Chain Reaction; RNA