Increase in laminin expression in allergic airway remodelling and decrease by dexamethasone.
Lung expression of the extracellular matrix protein, laminin, and its receptor, laminin-1 receptor, were examined in a mouse model of asthma with airway remodelling. Ovalbumin (OVA) was administered to BALB/c mice, intraperitoneally on days 0 and 14, and intranasally periodically between days 14 and 75. The mice developed airway eosinophil and mononuclear inflammatory cell infiltration and fibrosis. On day 76, a marked increase in total laminin was seen in the airways of OVA-treated mice compared to controls by Western blot analysis. The increased laminin expression was detected immunocytochemically in the thickened subepithelial basement membrane and around airways and blood vessels. The OVA-treated mice showed increased expression of the alpha1, beta1, and gamma1 chains of the laminin-1 isoform in monocytes, macrophages and eosinophils infiltrating the airways. Laminin-1 receptor expression was increased in inflammatory and endothelial cells in the lungs of OVA-treated mice compared to controls. Treatment of OVA-sensitised/challenged mice with dexamethasone reduced airway expression of laminin and laminin-1 receptor in OVA-treated mice but not airway hyperresponsiveness to methacholine. Laminin deposition may be an important component of the airway remodelling observed in chronic allergic lung inflammation and is a process modulated by corticosteroids.
Dept of Medicine, University of Washington, Seattle, WA 98195-6523, USA.
P E
PE
Christie
M
M
Jonas
C H
CH
Tsai
E Y
EY
Chi
W R
WR
Henderson
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D001707:Biopsy, Needle; D015153:Blotting, Western; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004802:Eosinophilia / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D017474:Receptors, Laminin / Q000276:immunology* / Q000378:metabolism*; D012307:Risk Factors; D012680:Sensitivity and Specificity
D015415:Biomarkers; D017474:Receptors, Laminin; D003907:Dexamethasone