Serine protease inhibitor gabexate mesilate attenuates American cockroach–induced bronchial damage and inflammatory cytokine release

M. F. Lee, C. W. Chang, Miau-Yaun Wang, S. J. Lin, Yi Hsing Chen

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)338-345
Number of pages8
JournalJournal of Investigational Allergology and Clinical Immunology
Volume24
Issue number5
Publication statusPublished - 2014 Jan 1

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Gabexate
Serine Proteinase Inhibitors
Cockroaches
Allergens
Cytokines
Chemokine CCL2
Epithelial Cells
Inflammation
Interleukin-8
Chemokines
Messenger RNA
Peptide Hydrolases
Periplaneta
CC Chemokines
Serine Proteases
p38 Mitogen-Activated Protein Kinases
Granulocyte-Macrophage Colony-Stimulating Factor
Protease Inhibitors
Taiwan
Microscopy

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

@article{8248fb7b42fa4558ae66cc598a286f70,
title = "Serine protease inhibitor gabexate mesilate attenuates American cockroach–induced bronchial damage and inflammatory cytokine release",
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.",
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Serine protease inhibitor gabexate mesilate attenuates American cockroach–induced bronchial damage and inflammatory cytokine release. / Lee, M. F.; Chang, C. W.; Wang, Miau-Yaun; Lin, S. J.; Chen, Yi Hsing.

In: Journal of Investigational Allergology and Clinical Immunology, Vol. 24, No. 5, 01.01.2014, p. 338-345.

Research output: Contribution to journalArticle

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N2 - 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.

AB - 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.

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