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Calcium-Calmodulin Mediates House Dust Mite-Induced ERK Activation and IL-8 Production in Human Respiratory Epithelial Cells

 Myung Hyun Sohn  ;  Kyung Eun Lee  ;  Kyu-Earn Kim  ;  Jun Young Park  ;  Eun-Soo Kim  ;  Kyung-Won Kim 
 RESPIRATION, Vol.74(4) : 447-453, 2007 
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BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Won(김경원) ORCID logo https://orcid.org/0000-0003-4529-6135
Kim, Kyu Earn(김규언)
Kim, Eun Soo(김은수)
Park, Jun Young(박준영)
Sohn, Myung Hyun(손명현) ORCID logo https://orcid.org/0000-0002-2478-487X
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