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Tissue inhibitor of metalloproteinase-1 modulates allergic lung inflammation in murine asthma.

ABSTRACT: Matrix metalloproteinases (MMPs) modulate development, inflammation, and repair in lungs. Tissue inhibitors of MMPs (TIMPs) interact with MMPs, controlling the intensity and nature of the response to injury. Absence of MMP-9, -2, and -8 activities is associated with altered lung inflammation during allergic sensitization. To test the hypothesis that the absence of TIMP-1 enhances allergic lung inflammation, airway hyperreactivity (AHR), and lung remodeling in asthma, we studied TIMP-1 null (TIMP-1 KO) mice and their WT controls using an ovalbumin (OVA) asthma model. TIMP-1 KO mice, compared to WT controls, developed an asthma phenotype characterized by AHR, pronounced cellular lung infiltrates, greater reduction in lung compliance, enhanced Th2 cytokine mRNA and protein expression, and altered collagen lung content associated with enhanced MMP-9 activity. Our findings support the hypothesis that TIMP-1 plays a protective role by preventing AHR and modulating inflammation, remodeling, and cytokine expression in an animal model of asthma.

SUBMITTER: Sands MF

PROVIDER: S-EPMC2676334 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Tissue inhibitor of metalloproteinase-1 modulates allergic lung inflammation in murine asthma.

Sands Mark F MF Ohtake Patricia J PJ Mahajan Supriya D SD Takyar Shervin S SS Aalinkeel Ravikumar R Fang Yisheng V YV Blume Jessica W JW Mullan Barbara A BA Sykes Don E DE Lachina Sandra S Knight Paul R PR Schwartz Stanley A SA

Clinical immunology (Orlando, Fla.) 20081026 2

Matrix metalloproteinases (MMPs) modulate development, inflammation, and repair in lungs. Tissue inhibitors of MMPs (TIMPs) interact with MMPs, controlling the intensity and nature of the response to injury. Absence of MMP-9, -2, and -8 activities is associated with altered lung inflammation during allergic sensitization. To test the hypothesis that the absence of TIMP-1 enhances allergic lung inflammation, airway hyperreactivity (AHR), and lung remodeling in asthma, we studied TIMP-1 null (TIMP ...[more]

PMID: 18955015

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Tissue inhibitor of metalloproteinase-1 modulates allergic lung inflammation in murine asthma.

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Tissue inhibitor of metalloproteinase-1 modulates allergic lung inflammation in murine asthma.

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