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

Mark F. Sands, Patricia J. Ohtake, Supriya D. Mahajan, Shervin S. Takyar, Ravikumar Aalinkeel, Yisheng V. Fang, Jessica W. Blume, Barbara A. Mullan, Don E. Sykes, Sandra Lachina, Paul R. Knight, Stanley A. Schwartz

Research output: Contribution to journalArticle

21 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)186-198
Number of pages13
JournalClinical Immunology
Volume130
Issue number2
DOIs
StatePublished - Feb 1 2009

Keywords

  • Airway remodeling
  • Asthma
  • Bronchial hyperreactivity
  • Intercellular matrix
  • MMPs
  • TIMP-1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Sands, M. F., Ohtake, P. J., Mahajan, S. D., Takyar, S. S., Aalinkeel, R., Fang, Y. V., Blume, J. W., Mullan, B. A., Sykes, D. E., Lachina, S., Knight, P. R., & Schwartz, S. A. (2009). Tissue inhibitor of metalloproteinase-1 modulates allergic lung inflammation in murine asthma. Clinical Immunology, 130(2), 186-198. https://doi.org/10.1016/j.clim.2008.08.029