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Role of Matrix‐metalloprotease‐7 in a Model of Experimental Asthma
Author(s) -
Goswami Sangeeta,
Barranco Wade,
Greenlee Kendra J,
Seryshev Alexander B,
Corry David B,
Kharadmand Farrah
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.671.3
Subject(s) - eotaxin , immunology , asthma , inflammation , matrix metalloproteinase , respiratory tract , respiratory epithelium , airway , mucus , lung , medicine , eosinophil , epithelium , biology , respiratory system , pathology , ecology , surgery
Bronchial asthma is a respiratory tract disease characterized by airway hyper‐responsiveness, mucus hyper‐production and inflammation. Airway epithelial cells are the initial sites where allergens are recognized. However, the role of epithelial cells in modulation of airway inflammation is not fully understood. One critical group of enzymes that regulate inflammatory processes in the lung is Matrix metalloproteases (MMP). We hypothesize that epithelial specific MMP7 modulates asthmatic phenotype by modifying inflammatory mediators produced by airway epithelium. We found that MMP7 null mice had reduced airway hyper‐reactivity in response to allergen challenge as well as fewer eosinophils in broncho‐alveolar lavage (BAL) fluid compared to WT mice. IL‐25 and Eotaxin, the critical mediators for asthma phenotype, were also reduced in MMP7−/− mice. Proteomic analysis of BAL fluid identified that Retinaldehydrogenase‐1 (RALDH‐1), a rate limiting epithelial specific enzyme for retinoic acid production, was up regulated in MMP7−/− asthmatic mice. In vivo inhibition of RALDH‐1, increased eotaxin protein expression in the airway and rescued the asthma phenotype in MMP7 −/− mice. Together, our data supports the role of MMP7 in modifying airway inflammation in asthma. We propose that identifying in vivo substrates for MMP7 may provide novel therapeutics for treatment of asthma. This work is funded by NIH grant (U19AI070973) to FK.