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Am J Physiol Lung Cell Mol Physiol 291: L265-L271, 2006; doi:10.1152/ajplung.00305.2005
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Reduced peribronchial fibrosis in allergen-challenged MMP-9-deficient mice

Dae Hyun Lim,1,2 Jae Youn Cho,1 Marina Miller,1 Kirsti McElwain,1 Shauna McElwain,1 and David H. Broide1

1Department of Medicine, University of California San Diego, La Jolla, California; and 2Department of Pediatrics, Inha University, School of Medicine, Incheon, Korea

Submitted 13 July 2005 ; accepted in final form 13 February 2006

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.

eosinophil; airway remodeling; smooth muscle; transforming growth factor-beta1; matrix metalloproteinase-9



Address for reprint requests and other correspondence: D. Broide, Univ. of California San Diego, Basic Science Bldg., Rm. 5090, 9500 Gilman Dr., La Jolla, CA 92093-0635 (e-mail: dbroide{at}ucsd.edu)




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