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The role of the extracellular matrix protein mindin in airway response to environmental airways injury.

Publication ,  Journal Article
Frush, S; Li, Z; Potts, EN; Du, W; Eu, JP; Garantziotis, S; He, Y-W; Foster, WM; Hollingsworth, JW
Published in: Environ Health Perspect
October 2011

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: We hypothesized that mindin would contribute to airways disease after inhalation of either lipopolysaccharide (LPS) or ozone. 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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Published In

Environ Health Perspect

DOI

EISSN

1552-9924

Publication Date

October 2011

Volume

119

Issue

10

Start / End Page

1403 / 1408

Location

United States

Related Subject Headings

  • Toxicology
  • Toll-Like Receptor 4
  • Ozone
  • Neutrophil Infiltration
  • Mice, Mutant Strains
  • Mice, Inbred C57BL
  • Mice
  • Lipopolysaccharides
  • Immunity, Innate
  • Extracellular Matrix Proteins
 

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Frush, S., Li, Z., Potts, E. N., Du, W., Eu, J. P., Garantziotis, S., … Hollingsworth, J. W. (2011). The role of the extracellular matrix protein mindin in airway response to environmental airways injury. Environ Health Perspect, 119(10), 1403–1408. https://doi.org/10.1289/ehp.1003339
Frush, Sarah, Zhuowei Li, Erin N. Potts, Wanglei Du, Jerry P. Eu, Stavros Garantziotis, You-Wen He, W Michael Foster, and John W. Hollingsworth. “The role of the extracellular matrix protein mindin in airway response to environmental airways injury.Environ Health Perspect 119, no. 10 (October 2011): 1403–8. https://doi.org/10.1289/ehp.1003339.
Frush S, Li Z, Potts EN, Du W, Eu JP, Garantziotis S, et al. The role of the extracellular matrix protein mindin in airway response to environmental airways injury. Environ Health Perspect. 2011 Oct;119(10):1403–8.
Frush, Sarah, et al. “The role of the extracellular matrix protein mindin in airway response to environmental airways injury.Environ Health Perspect, vol. 119, no. 10, Oct. 2011, pp. 1403–08. Pubmed, doi:10.1289/ehp.1003339.
Frush S, Li Z, Potts EN, Du W, Eu JP, Garantziotis S, He Y-W, Foster WM, Hollingsworth JW. The role of the extracellular matrix protein mindin in airway response to environmental airways injury. Environ Health Perspect. 2011 Oct;119(10):1403–1408.

Published In

Environ Health Perspect

DOI

EISSN

1552-9924

Publication Date

October 2011

Volume

119

Issue

10

Start / End Page

1403 / 1408

Location

United States

Related Subject Headings

  • Toxicology
  • Toll-Like Receptor 4
  • Ozone
  • Neutrophil Infiltration
  • Mice, Mutant Strains
  • Mice, Inbred C57BL
  • Mice
  • Lipopolysaccharides
  • Immunity, Innate
  • Extracellular Matrix Proteins