Interleukin-13-Dependent Expression of Matrix Metalloproteinase-12 Is Required for the Development of Airway Eosinophilia in Mice

Mahmoud A. Pouladi, Clinton S. Robbins, Filip K. Swirski, Meghan Cundall, Andrew N.J. McKenzie, Manel Jordana, Steven D. Shapiro, Martin R. Stämpfli

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44 Scopus citations

Abstract

We investigated the expression and function of matrix metalloproteinase-12 (MMP-12) in a model of allergic airway inflammation. Mice were sensitized mucosally by exposure to aerosolized ovalbumin (OVA) daily over a period of 10 d in the context of adenovirus-mediated granulocyte macrophage colony-stimulating factor (CM-CSF) expression. The ensuing inflammatory response is characterized by a Th2 cytokine profile, OVA-specific IgE, and airway eosinophilia. Using real-time, quantitative reverse transcriptase- polymerase chain reaction we assessed MMP-12 mRNA expression in whole lung tissue. We observed a 12- and 70-fold increase in expression at Days 7 and 11, respectively, in OVA-exposed mice when compared with naive controls. Immunoblot analysis revealed an increase in MMP-12 protein in the bronchoalveolar lavage fluid of mice exposed to OVA in the context of CM-CSF. No such elevation was observed in mice exposed to saline only in the context of CM-CSF. To assess functional role of MMP-12, MMP-12 knockout (KO) mice were subjected to the aforementioned protocol. We observed an 80% reduction in eosinophils in the bronchoalveolar lavage fluid of KO mice compared with their wild-type littermates. Using interleukin-13 KO mice, we demonstrated that expression of MMP-12 is interleukin-13-dependent. Collectively, our data indicate a novel function for MMP-12 in the process of airway eosinophil accumulation.

Original languageEnglish
Pages (from-to)84-90
Number of pages7
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume30
Issue number1
DOIs
StatePublished - Jan 2004

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