title: Serine protease inhibitor gabexate mesilate attenuates american cockroach-induced bronchial damage and inflammatory cytokine release.
abstract: OBJECTIVE
  Allergic airway diseases are not only a T,2-mediated chronic airway inflammation, but also a condition of epithelial barrier defects and dysfunction. Allergens with protease activities are known factors that initiate respiratory epithelial damage. Cockroach allergy is the second leading cause of allergic respiratory airway diseases in Taiwan, and cockroach allergens have strong serine protease activity. This study aimed to determine the protective effect of the direct local administration of gabexate mesilate (GM) on American cockroach allergen (CraA)-induced human bronchial epithelial cell inflammation.
  
  
  METHODS
  BEAS-2B cells, from the human bronchial epithelial cell line, were stimulated with CraA or co-cultured with different doses of GM. Cellular morphologic changes were observed by microscopy and changes in chemokine mRNA expression and protein levels were determined by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and ELISA. Effects of specific inhibitors of ERK1/2 (U0126), INK (SP600125), and p38 MAPK (SB203580) on CraA-induced chemokine mRNA expression were also tested by RT-PCR.
  
  
  RESULTS
  GM prevented CraA-induced bronchial epithelial cell detachment and morphological changes. It had superior and more extensive suppression effects than specific target MAPK inhibitors in CraA-induced mRNA expression of IL-8, monocyte chemotactic protein (MCP) 1, chemokine (C-C motif) ligand 20, and granulocyte-macrophage colony-stimulating factor from the cells in a dose-dependent manner. CraA-induced IL-8 and MCP-1 protein production from BEAS-2B cells was also attenuated by GM.
  
  
  CONCLUSIONS
  The serine protease inhibitor GM has local protective effects against CraA-induced bronchial epithelial inflammation. The development of an inhaled or intranasal protease inhibitor may be a potential strategy for the treatment of allergic airway diseases induced by allergens with protease activities.
authors.forename: M F
authors.initials: MF
authors.lastname: Lee
authors.forename: C W
authors.initials: CW
authors.lastname: Chang
authors.forename: N M
authors.initials: NM
authors.lastname: Wang
authors.forename: S J
authors.initials: SJ
authors.lastname: Lin
authors.forename: Y H
authors.initials: YH
authors.lastname: Chen
mesh_terms: D000818:Animals; D001980:Bronchi / Q000473:pathology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis; D018925:Chemokines / Q000235:genetics; D003058:Cockroaches / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000473:pathology; D016670:Gabexate / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018925:Chemokines; D016207:Cytokines; D016209:Interleukin-8; D015842:Serine Proteinase Inhibitors; D016670:Gabexate; D020928:Mitogen-Activated Protein Kinases