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ASK1 deficiency attenuates hyperoxia‐induced inflammation and cell apoptosis in the lung
Author(s) -
Fukumoto Jutaro,
Hosseinian Nima,
Priyanshi Patel,
Cho Young,
R. Cox Ruan,
Lakshimi Galam,
Soundararajan Ramani,
F. Lockey Richard,
Kolliputi Narasaiah
Publication year - 2015
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.29.1_supplement.1046.1
Subject(s) - ask1 , proinflammatory cytokine , hyperoxia , apoptosis , bronchoalveolar lavage , inflammation , oxidative stress , tunel assay , lung , immunology , kinase , biology , medicine , protein kinase a , microbiology and biotechnology , endocrinology , biochemistry , mitogen activated protein kinase kinase
Rationale Apoptosis signal‐regulating kinase 1 (ASK1), a member of the MAPK kinase (MAP3K) family, is activated by various stimuli including oxidative stress, ER stress, and DNA damage. Inspiration of high oxygen fraction is a palliative therapy to counteract acute lung injury (ALI). Our previous data indicates that ASK1 plays a critical role in this process. However, it is unclear whether or not deletion of ASK1 in vivo protects against HALI. We investigated whether ASK1 deletion would lead to protection against HALI.Methods ASK1 KO mice and control littermates were exposed to 100% oxygen for 48‐72 hours and euthanized to collect bronchoalveolar lavage (BAL) fluid for cell counts and cytokine measurements, and lung tissue collected for assessment of lung epithelial cell apoptosis. Results BAL fluid analysis revealed a significant decrease in IL‐1β level in KO mice. Differential cell count shows suppressed inflammatory cell infiltration in KO mice. Lung epithelial cell apoptosis was attenuated in ASK1 KO mice compared to WT mice as determined by TUNEL staining. Moreover, ASK1 KO mice exhibited significant increase in protein concentration in BAL fluid. Conclusion ASK1 has a proinflammatory profile. Meanwhile, the permeability increase was observed in ASK1 KO mice which indicate that hyperoxia‐induced increase in permeability is independent of ASK1. Our data suggest that ASK1 can be a novel molecular target for ALI treatment. Funding source: This work was funded by the American Heart Association National Scientist Development Grant 09SDG2260957 and National Institutes of Health R01 HL105932 and the Joy McCann Culverhouse Endowment to the Division of Allergy and Immunology.