Abstract | BACKGROUND: Our previous work demonstrated that the extracellular matrix protein mindin contributes to allergic airways disease. However, the role of mindin in nonallergic airways disease has not previously been explored. OBJECTIVES: METHODS: We exposed C57BL/6J and mindin-deficient (-/-) mice to aerosolized LPS (0.9 μg/m3 for 2.5 hr), saline, ozone (1 ppm for 3 hr), or filtered air (FA). All mice were evaluated 4 hr after LPS/saline exposure or 24 hr after ozone/FA exposure. We characterized the physiological and biological responses by analysis of airway hyperresponsiveness (AHR) with a computer-controlled small-animal ventilator (FlexiVent), inflammatory cellular recruitment, total protein in bronchoalveolar lavage fluid (BALF), proinflammatory cytokine profiling, and ex vivo bronchial ring studies. RESULTS: After inhalation of LPS, mindin-/- mice demonstrated significantly reduced total cell and neutrophil recruitment into the airspace compared with their wild-type counterparts. Mindin-/- mice also exhibited reduced proinflammatory cytokine production and lower AHR to methacholine challenge by FlexiVent. After inhalation of ozone, mice had no detectible differences in cellular inflammation or total BALF protein dependent on mindin. However, mindin-/- mice were protected from increased proinflammatory cytokine production and AHR compared with their C57BL/6J counterparts. After ozone exposure, bronchial rings derived from mindin-/- mice demonstrated reduced constriction in response to carbachol. CONCLUSIONS: These data demonstrate that the extracellular matrix protein mindin modifies the airway response to both LPS and ozone. Our data support a conserved role of mindin in production of proinflammatory cytokines and the development of AHR in two divergent models of reactive airways disease, as well as a role of mindin in airway smooth muscle contractility after exposure to ozone.
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Authors | Sarah Frush, Zhuowei Li, Erin N Potts, Wanglei Du, Jerry P Eu, Stavros Garantziotis, You-Wen He, W Michael Foster, John W Hollingsworth |
Journal | Environmental health perspectives
(Environ Health Perspect)
Vol. 119
Issue 10
Pg. 1403-8
(Oct 2011)
ISSN: 1552-9924 [Electronic] United States |
PMID | 21684833
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Retracted Publication)
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Chemical References |
- Extracellular Matrix Proteins
- Lipopolysaccharides
- Toll-Like Receptor 4
- mindin
- Ozone
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Topics |
- Animals
- Bronchial Hyperreactivity
(chemically induced, immunology)
- Extracellular Matrix Proteins
(genetics, metabolism)
- Immunity, Innate
- Lipopolysaccharides
(toxicity)
- Mice
- Mice, Inbred C57BL
- Mice, Mutant Strains
- Neutrophil Infiltration
(drug effects)
- Ozone
(toxicity)
- Toll-Like Receptor 4
(metabolism)
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