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Ozone induces pulmonary activating transcription factor 3 (ATF3) expression
Author(s) -
Wu Yuchieh,
Konsavage Wesley,
Floros Joanna,
Shenberger Jeffrey S
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.1037.2
Subject(s) - atf3 , activating transcription factor , inflammation , atf4 , phosphorylation , p38 mitogen activated protein kinases , transcription factor , oxidative stress , signal transduction , integrated stress response , mapk/erk pathway , chemistry , immunology , biology , medicine , microbiology and biotechnology , endocrinology , gene expression , promoter , messenger rna , biochemistry , gene , translation (biology)
Ozone, a major component of air pollution, has been linked to detrimental health effects including inflammation, asthma, cardiovascular disease, and increased mortality. While recent evidence suggests that transcription factor ATF3 is a negative regulator of pulmonary inflammation, its role in O 3 ‐induced lung injury remains unknown. To address this question, we exposed 8‐10 wk male C57BL/6 mice to 2 ppm O 3 or filtered air (FA) for 3 hrs and allowed subsequent recovery in room air for up to 24 hrs. Compared to FA, ATF3 protein was up‐regulated by 5‐fold after exposure to O 3 for 3 hrs (p<0.01) while the expression of ATF4 and ATF5 proteins remained unchanged. O 3 increased the nuclear accumulation of ATF3, but not ATF4. Quantitative PCR revealed a 3‐fold increase in ATF3 after O 3 but no change in ATF4 or ATF5. Both ATF3 protein and mRNA levels remained elevated during early recovery (4 hrs post‐exposure), but declined by 24 hrs. Induction of ATF3 expression involves multiple overlapping signal transduction pathways known to be sensitive to oxidative stress. We found that O 3 increased the phosphorylation of ERK1/2, JNK, and p38 MAPK, but not the phosphorylation of eIF2α. In addition, p38 phosphorylation remained elevated during early recovery. Altogether, these results illustrate that O 3 induces expression of ATF3 in the lung. The increase in ATF3 may play a role in the negative regulation of O 3 ‐induced inflammation.