Divergent functions for airway epithelial matrix metalloproteinase 7 and retinoic acid in experimental asthma

Sangeeta Goswami; Pornpimon Angkasekwinai; Ming Shan; Kendra J Greenlee; Wade T Barranco; Sumanth Polikepahad; Alexander Seryshev; Li-zhen Song; David Redding; Bhupinder Singh; Sanjiv Sur; Prescott Woodruff; Chen Dong; David B Corry; Farrah Kheradmand

doi:10.1038/ni.1719

Divergent functions for airway epithelial matrix metalloproteinase 7 and retinoic acid in experimental asthma

Nat Immunol. 2009 May;10(5):496-503. doi: 10.1038/ni.1719. Epub 2009 Mar 29.

Authors

Sangeeta Goswami¹, Pornpimon Angkasekwinai, Ming Shan, Kendra J Greenlee, Wade T Barranco, Sumanth Polikepahad, Alexander Seryshev, Li-zhen Song, David Redding, Bhupinder Singh, Sanjiv Sur, Prescott Woodruff, Chen Dong, David B Corry, Farrah Kheradmand

Affiliation

¹ Department of Immunology, Baylor College of Medicine, Houston, Texas, USA.

PMID: 19329997
PMCID: PMC5298936
DOI: 10.1038/ni.1719

Abstract

The innate immune response of airway epithelial cells to airborne allergens initiates the development of T cell responses that are central to allergic inflammation. Although proteinase allergens induce the expression of interleukin 25, we show here that epithelial matrix metalloproteinase 7 (MMP7) was expressed during asthma and was required for the maximum activity of interleukin 25 in promoting the differentiation of T helper type 2 cells. Allergen-challenged Mmp7(-/-) mice had less airway hyper-reactivity and production of allergic inflammatory cytokines and higher expression of retinal dehydrogenase 1. Inhibition of retinal dehydrogenase 1 restored the asthma phenotype of Mmp7(-/-) mice and inhibited the responses of lung regulatory T cells, whereas exogenous administration of retinoic acid attenuated the asthma phenotype. Thus, MMP7 coordinates allergic lung inflammation by activating interleukin 25 while simultaneously inhibiting retinoid-dependent development of regulatory T cells.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Allergens / immunology
Animals
Asthma / immunology
Asthma / metabolism*
Asthma / pathology
Bronchoalveolar Lavage Fluid / chemistry
Bronchoalveolar Lavage Fluid / cytology
Bronchoalveolar Lavage Fluid / immunology
Cell Differentiation / immunology
Chromatography, High Pressure Liquid
Cytokines / biosynthesis
Cytokines / immunology
Disease Models, Animal
Electrophoresis, Gel, Two-Dimensional
Humans
Immunohistochemistry
Interleukins / immunology
Interleukins / metabolism*
Lymphocyte Activation / immunology
Matrix Metalloproteinase 7 / immunology
Matrix Metalloproteinase 7 / metabolism*
Mice
Mice, Inbred C57BL
Mice, Knockout
Proteomics
Respiratory Mucosa / immunology
Respiratory Mucosa / metabolism*
Retinal Dehydrogenase / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Th2 Cells / cytology
Th2 Cells / immunology
Tretinoin / immunology
Tretinoin / metabolism*

Substances

Allergens
Cytokines
Interleukins
Mydgf protein, mouse
Tretinoin
Retinal Dehydrogenase
Matrix Metalloproteinase 7

Abstract

Publication types

MeSH terms

Substances

Grants and funding