Reduced peribronchial fibrosis in allergen-challenged MMP-9-deficient mice.
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.
Lim
Dae Hyun
DH
Department of Medicine, University of California San Diego, La Jolla, 92093, USA.
Cho
Jae Youn
JY
Miller
Marina
M
McElwain
Kirsti
K
McElwain
Shauna
S
Broide
David H
DH
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
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