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Expression of TLR9 in mouse and human lung and its role in lung inflammation in chicken barn air exposure
Author(s) -
Schneberger David,
Aulakh Gurpreet,
Channabasappa Shankaramurthy,
Caldwell Sarah,
Singh Baljit
Publication year - 2011
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.25.1_supplement.952.5
Subject(s) - tlr9 , lung , inflammation , immune system , tlr4 , biology , barn , immunology , respiratory system , pathology , in situ hybridization , innate immune system , medicine , gene expression , gene , anatomy , biochemistry , civil engineering , dna methylation , engineering
Workers exposed to intensive animal housing facility air show signs of occupationally‐related lung dysfunction. These respiratory symptoms are associated with endotoxin, but within these environments gram negative bacteria may constitute only a small portion of the microorganisms present. In contrast, unmethylated DNA can be found in all bacteria, some viruses, and mould. Immune responses to this unmethylated DNA are mediated through the TLR9 receptor. Therefore, we sought to test expression of TLR9 in mouse as well as human lungs, to see if mice would be an appropriate model for an exposure study. We hypothesized that the immune response seen in the lungs of mice exposed to barn air would be altered in a TLR9‐deficient animal towards a less inflammatory state. We used immunohistology, immuno‐electron microscopy and in situ hybridization to show expression of TLR9 on bronchial epithelium, alveolar septal cells, and alveolar macrophage of mouse and human lungs. Having established similar receptor expression, a barn exposure study was done using a TLR9‐deficient mouse model. Mice were exposed to chicken barn air for 8 hours/day for 1, 5, or 20 days. Examination of bronchiolar lavage and serum against a panel of cytokines (IL‐1β, IL‐6, IL‐10, IL‐12, TNF‐α, and IFN‐γ) showed no significant differences after one day exposure. TNF‐α (p=0.06) levels in TLR9‐deficient mice were reduced in blood and lavage fluids after 5 days, and somewhat reduced at 20 days of exposure (p=0.14), while IFN‐γ was also reduced at 5 days(p=0.06) and remained reduced after 20 days (p=0.05). A reduction in lung neutrophils at 20 days was also seen. Our data shows similar expression patterns of TLR9 in mouse and human lungs, and that barn dust DNA may contribute to inflammation induced following exposure to chicken barn air. Grant Funding Source : NSERC