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Original Article
 

Serine Protease Inhibitor Gabexate Mesilate Attenuates American Cockroach–Induced Bronchial Damage and Inflammatory Cytokine Release
 

MF Lee,1 CW Chang,2 NM Wang,2 SJ Lin,3 YH Chen4,5

1Department of Medical Research, Taichung Veterans General Hospital, and General Education Center, Tunghai University, Taichung, Taiwan
2Institute of Biotechnology, National Changhua University of Education, Changhua, Taiwan
3School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan
4Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan
5Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan

J Investig Allergol Clin Immunol 2014; Vol. 24(5): 338-345
 

 Abstract


Background and objective: Allergic airway diseases are not only a TH2-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), JNK (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.

Key words: Cockroach allergy. Bronchial epithelial cells. Serine protease inhibitor. Gabexate mesilate.