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Lung and Blood Gene Expression Profiles from Cynomolgus Monkeys Exposed to Ozone
Author(s) -
Kourteva Galina Tzoneva,
Hilton Holly,
Wei Xin,
Li Ying L,
March Thomas,
Benson Janet,
Rosinski James A,
Hicks Alexandra
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.22.2_supplement.212
Subject(s) - inflammation , immunology , copd , chemokine , lung , biology , cancer research , medicine
Exposure to ozone has been implicated in the pathology of COPD and evokes a neutrophilic inflammation in airways. It has been used for assessing anti‐inflammatory drugs in early clinical development. There is interest in using primates as a preclinical mechanistic model of ozone‐evoked lung inflammation. Here we characterize gene expression profiles of lung and blood from monkeys exposed to ozone to validate this model. METHODS: 12 monkeys were exposed by to 1 ppm ozone or filtered air for 6 hours. Lung and blood samples were run on Affymetrix Rhesus microarrays. Analysis of covariance and a list of genes with p <= 0.05 was used for pathway analysis in Ingenuity & MetaCore. RESULTS: The major pathways activated by ozone challenge were oxidative phosphorylation, ubiquinone biosynthesis, protein ubiquitination, TGF signaling, IL2, IL4, cell adhesion, integrin & chemokine signaling and T cell receptor signaling, consistent with an inflammatory response. MMP9, p65, AP‐1, HDAC8, FOSL2, MAPKK5, MAPK11, MAPK12, SYK, IL8, IL10RA, SERPINE1, SERPINE8 & Cytochrome C oxidases were significantly modified by ozone challenge as reported in human ozone responses and COPD. CONCLUSIONS: These genomic data demonstrate that ozone challenge induces pulmonary inflammation via activation of ozone‐ & COPD‐associated inflammatory pathways. These data support the preclinical use of the primate ozone‐evoked lung inflammation model.