German Cockroach Extract Induces Matrix Metalloproteinase-1 Expression, Leading to Tight Junction Disruption in Human Airway Epithelial Cells
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Purpose: Cockroach exposure is a pivotal cause of asthma. Tight junctions are intercellular structures required for maintenanceof the barrier function of the airway epithelium, which is impaired in this disease. Matrix metalloproteinases (MMPs) digest extracellularmatrix components and are involved in asthma pathogenesis: MMP1 is a collagenase with a direct influence on airwayobstruction in asthmatics. This study aimed to investigate the mechanism by which German cockroach extract (GCE) inducesMMP1 expression and whether MMP1 release alters cellular tight junctions in human airway epithelial cells (NCI-H292). Materials and Methods: mRNA and protein levels were determined using real-time PCR and ELISA. Tight junction proteins weredetected using immunofluorescence staining. Epithelial barrier function was measured by transepithelial electrical resistance(TEER). The binding of a transcription factor to DNA molecules was determined by electrophoretic mobility shift assay, while thelevels of tight junction proteins and phosphorylation were determined using Western blotting. Results: GCE was shown to increase MMP1 expression, TEER, and tight junction degradation. Both an inhibitor and small interferingRNA (siRNA) of MMP1 significantly decreased GCE-induced tight junction disruption. Furthermore, transient transfectionwith ETS1 and SP1 siRNA, and anti-TLR2 antibody pretreatment prevented MMP1 expression and tight junction degradation. Anextracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) inhibitor also blocked MMP1 release, ETS1/SP1 DNA binding, and tight junction alteration. Conclusion: GCE treatment increases MMP1 expression, leading to tight junction disruption, which is transcriptionally regulatedand influenced by the ERK/MAPK pathway in airway epithelial cells. These findings may contribute to developing novel therapeuticstrategies for airway diseases.
Abstract
Purpose: Cockroach exposure is a pivotal cause of asthma. Tight junctions are intercellular structures required for maintenanceof the barrier function of the airway epithelium, which is impaired in this disease. Matrix metalloproteinases (MMPs) digest extracellularmatrix components and are involved in asthma pathogenesis: MMP1 is a collagenase with a direct influence on airwayobstruction in asthmatics. This study aimed to investigate the mechanism by which German cockroach extract (GCE) inducesMMP1 expression and whether MMP1 release alters cellular tight junctions in human airway epithelial cells (NCI-H292). Materials and Methods: mRNA and protein levels were determined using real-time PCR and ELISA. Tight junction proteins weredetected using immunofluorescence staining. Epithelial barrier function was measured by transepithelial electrical resistance(TEER). The binding of a transcription factor to DNA molecules was determined by electrophoretic mobility shift assay, while thelevels of tight junction proteins and phosphorylation were determined using Western blotting. Results: GCE was shown to increase MMP1 expression, TEER, and tight junction degradation. Both an inhibitor and small interferingRNA (siRNA) of MMP1 significantly decreased GCE-induced tight junction disruption. Furthermore, transient transfectionwith ETS1 and SP1 siRNA, and anti-TLR2 antibody pretreatment prevented MMP1 expression and tight junction degradation. Anextracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) inhibitor also blocked MMP1 release, ETS1/SP1 DNA binding, and tight junction alteration. Conclusion: GCE treatment increases MMP1 expression, leading to tight junction disruption, which is transcriptionally regulatedand influenced by the ERK/MAPK pathway in airway epithelial cells. These findings may contribute to developing novel therapeuticstrategies for airway diseases.
참고문헌 (40)
- Lombardi C, "Is allergic sensitization relevant in severe asthma? Which allergens may be culprit?", World Allergy Organ J, 10, pp.2~ (2017)
- 손명현, "The Cockroach and Allergic Diseases", Allergy, Asthma & Immunology Research, 4(5), pp.264~269 (2012), 대한천식알레르기학회[DOI]
- O’Hollaren MT, "Exposure to an aeroallergen as a possible precipitating factor in respiratory arrest in young patients with asthma", N Engl J Med, 324, pp.359~363 (1991)
- Rosenstreich DL, "The role of cockroach allergy and exposure to cockroach allergen in causing morbidity among inner-city children with asthma", N Engl J Med, 336, pp.1356~1363 (1997)
- Page K, "Role of cockroach proteases in allergic disease", Curr Allergy Asthma Rep, 12, pp.448~455 (2012)
- Yong TS, "Identification and purification of IgE-reactive proteins in German cockroach extract", Yonsei Med J, 40, pp.283~289 (1999)
- Page K, "TLR2-mediated activation of neutrophils in response to German cockroach frass", J Immunol, 180, pp.6317~6324 (2008)
- Hughes VS, "German cockroach frass proteases cleave pro-matrix metalloproteinase-9", Exp Lung Res, 33, pp.135~150 (2007)
- Vandenbroucke RE, "A therapeutic role for matrix metalloproteinase inhibitors in lung diseases?", Eur Respir J, 38, pp.1200~1214 (2011)
- Grzela K, "Asthma-from childhood asthma to ACOS phenotypes", pp.41~69 (2016), InTech
- Fingleton B, "MMPs as therapeutic targets--still a viable option?", Semin Cell Dev Biol, 19, pp.61~68 (2008)
- Suzuki R, "Matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in sputum from patients with bronchial asthma", J Asthma, 38, pp.477~484 (2001)
- Royce SG, "Mesenchymal stem cells and serelaxin synergistically abrogate established airway fibrosis in an experimental model of chronic allergic airways disease", Stem Cell Res, 15, pp.495~505 (2015)
- Stephen T Holgate, "A Brief History of Asthma and Its Mechanisms to Modern Concepts of Disease Pathogenesis", Allergy, Asthma & Immunology Research, 2(3), pp.165~171 (2010), 대한천식알레르기학회
- Loxham M, "Epithelial function and dysfunction in asthma", Clin Exp Allergy, 44, pp.1299~1313 (2014)
- Shin K, "Tight junctions and cell polarity", Annu Rev Cell Dev Biol, 22, pp.207~235 (2006)
- Holgate ST, "Epithelium dysfunction in asthma", J Allergy Clin Immunol, 120, pp.1233~1244 (2007)
- Holgate ST, "The airway epithelium is central to the pathogenesis of asthma", Allergol Int, 57, pp.1~10 (2008)
- Vermeer PD, "MMP9 modulates tight junction integrity and cell viability in human airway epithelia", Am J Physiol Lung Cell Mol Physiol, 296, pp.L751~L762 (2009)
- Rogers NK, "Extra-cellular matrix proteins induce matrix metalloproteinase-1 (MMP-1) activity and increase airway smooth muscle contraction in asthma", PLoS One, 9, pp.e90565~ (2014)
- Yan C, "Regulation of matrix metalloproteinase gene expression", J Cell Physiol, 211, pp.19~26 (2007)
- Hadler-Olsen E, "Regulation of matrix metalloproteinase activity in health and disease", FEBS J, 278, pp.28~45 (2011)
- Antony AB, "Cockroach extract antigen increases bronchial airway epithelial permeability", J Allergy Clin Immunol, 110, pp.589~595 (2002)
- Grzela K, "Airway remodeling in chronic obstructive pulmonary disease and asthma : the role of matrix metalloproteinase-9", Arch Immunol Ther Exp(Warsz), 64, pp.47~55 (2016)
- Erlewyn-Lajeunesse MD, "Bronchoalveolar lavage MMP-9 and TIMP1 in preschool wheezers and their relationship to persistent wheeze", Pediatr Res, 64, pp.194~199 (2008)
- Karakoc GB, "Exhaled breath condensate MMP-9 level and its relationship wıth asthma severity and interleukin-4", 10 levels in children, 2012, pp.108, 300~304
- Rajah R, "Elevated levels of the IGF-binding protein protease MMP-1 in asthmatic airway smooth muscle", Am J Respir Cell Mol Biol, 20, pp.199~208 (1999)
- Dolhnikoff M, "The outer wall of small airways is a major site of remodeling in fatal asthma", J Allergy Clin Immunol, 123, pp.1090~1097 (2009)
- Wan H, "Quantitative structural and biochemical analyses of tight junction dynamics following exposure of epithelial cells to house dust mite allergen Der p 1", Clin Exp Allergy, 30, pp.685~698 (2000)
- Blume C, "Barrier responses of human bronchial epithelial cells to grass pollen exposure", Eur Respir J, 42, pp.87~97 (2013)
- Nhu QM, "Novel signaling interactions between proteinase-activated receptor 2 and Toll-like receptors in vitro and in vivo", Mucosal Immunol, 3, pp.29~39 (2010)
- Rallabhandi P, "Analysis of proteinase-activated receptor 2 and TLR4 signal transduction : a novel paradigm for receptor cooperativity", J Biol Chem, 283, pp.24314~24325 (2008)
- Segura-Valdez L, "Upregulation of gelatinases A and B, collagenases 1 and 2, and increased parenchymal cell death in COPD", Chest, 117, pp.684~694 (2000)
- Imai K, "Human collagenase (matrix metalloproteinase-1) expression in the lungs of patients with emphysema", Am J Respir Crit Care Med, 163(3 Pt 1), pp.786~791 (2001)
- Cataldo DD, "Matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases mRNA transcripts in the bronchial secretions of asthmatics", Lab Invest, 84, pp.418~424 (2004)
- Xiao C, "Defective epithelial barrier function in asthma", J Allergy Clin Immunol, 128, pp.549~556 (2011)
- Rutter JL, "A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter creates an Ets binding site and augments transcription", Cancer Res, 58, pp.5321~5325 (1998)
- Liu T, "Matrix metalloproteinase-1 induction by diethyldithiocarbamate is regulated via Akt and ERK", miR222, Biosci Rep, pp.2016, 36[DOI]
- Wallace AM, "Functional characterization of the matrix metalloproteinase-1 cigarette smoke-responsive region and association with the lung health study", Respir Res, 13, pp.79~ (2012)
- Redecke V, "Cutting edge : activation of Toll-like receptor 2 induces a Th2 immune response and promotes experimental asthma", J Immunol, 172, pp.2739~2743 (2004)