title: Calcium-calmodulin mediates house dust mite-induced ERK activation and IL-8 production in human respiratory epithelial cells.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Pediatrics and Institute of Allergy, BK21 Project for Medical Science, Biomolecule Secretion Research Center, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Myung Hyun
authors.initials: MH
authors.lastname: Sohn
authors.forename: Kyung Eun
authors.initials: KE
authors.lastname: Lee
authors.forename: Kyung-Won
authors.initials: KW
authors.lastname: Kim
authors.forename: Eun-Soo
authors.initials: ES
authors.lastname: Kim
authors.forename: Jun Young
authors.initials: JY
authors.lastname: Park
authors.forename: Kyu-Earn
authors.initials: KE
authors.lastname: Kim
mesh_terms: D000485:Allergens / Q000009:adverse effects*; D000818:Animals; D015153:Blotting, Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D040001:Dermatophagoides farinae / Q000276:immunology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005419:Flavonoids; D015870:Gene Expression / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D012313:RNA / Q000235:genetics; D020545:Respiratory Mucosa / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000485:Allergens; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D016209:Interleukin-8; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; C031938:calmidazolium; D004533:Egtazic Acid; D012313:RNA; D019833:Genistein; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one