title: Reduced peribronchial fibrosis in allergen-challenged MMP-9-deficient mice.
abstract: Matrix metalloproteinases (MMPs) are a family of extracellular proteases that are responsible for the degradation of the extracellular matrix during tissue remodeling. We have used a mouse model of allergen-induced airway remodeling to determine whether MMP-9 plays a role in airway remodeling. MMP-9-deficient and wild-type (WT) mice were repetitively challenged intranasally with ovalbumin (OVA) antigen to develop features of airway remodeling including peribronchial fibrosis and increased thickness of the peribronchial smooth muscle layer. OVA-challenged MMP-9-deficient mice had less peribronchial fibrosis and total lung collagen compared with OVA-challenged WT mice. There was no reduction in mucus expression, smooth muscle thickness, or airway responsiveness in OVA-challenged MMP-9-deficient compared with OVA-challenged WT mice. OVA-challenged MMP-9-deficient mice had reduced levels of bronchoalveolar lavage (BAL) regulated on activation, normal T cell expressed, and secreted (RANTES), as well as reduced numbers of BAL and peribronchial eosinophils compared with OVA-challenged WT mice. There were no significant difference in levels of BAL eotaxin, thymus- and activation-regulated chemokine (TARC), or macrophage-derived chemokine (MDC) in OVA-challenged WT compared with MMP-9-deficient mice. Overall, this study demonstrates that MMP-9 may play a role in mediating selected aspects of allergen-induced airway remodeling (i.e., modest reduction in levels of peribronchial fibrosis) but does not play a significant role in mucus expression, smooth muscle thickness, or airway responsiveness.
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, 92093, USA.
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Lim
authors.forename: Jae Youn
authors.initials: JY
authors.lastname: Cho
authors.forename: Marina
authors.initials: M
authors.lastname: Miller
authors.forename: Kirsti
authors.initials: K
authors.lastname: McElwain
authors.forename: Shauna
authors.initials: S
authors.lastname: McElwain
authors.forename: David H
authors.initials: DH
authors.lastname: Broide
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D018925:Chemokines / Q000276:immunology; D005355:Fibrosis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009093:Mucus / Q000378:metabolism; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology; D053773:Transforming Growth Factor beta1
chemical_list: D000485:Allergens; D018925:Chemokines; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D010047:Ovalbumin; D020780:Matrix Metalloproteinase 9