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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2018.1
- 수록면
- 1,222 - 1,231 (10page)
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초록· 키워드
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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.
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참고문헌 (3)
참고문헌 신청
손명현 / 2012 / The Cockroach and Allergic Diseases / Allergy, Asthma & Immunology Research 4(5):264~269
Stephen T Holgate / 2010 / A Brief History of Asthma and Its Mechanisms to Modern Concepts of Disease Pathogenesis / Allergy, Asthma & Immunology Research 2(3):165~171
Imai K / 2001 / Human collagenase (matrix metalloproteinase-1) expression in the lungs of patients with emphysema / Am J Respir Crit Care Med 163(3 Pt 1):786~791
Stephen T Holgate / 2010 / A Brief History of Asthma and Its Mechanisms to Modern Concepts of Disease Pathogenesis / Allergy, Asthma & Immunology Research 2(3):165~171
Imai K / 2001 / Human collagenase (matrix metalloproteinase-1) expression in the lungs of patients with emphysema / Am J Respir Crit Care Med 163(3 Pt 1):786~791
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