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Suppressor of Cytokine Signaling‐1 Inhibits Hyperoxic Induced Inflammasome Activation
Author(s) -
Kolliputi Narasaiah,
Shaik Rahamthulla,
Waxman Aaron B
Publication year - 2010
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.24.1_supplement.796.1
Subject(s) - inflammasome , hyperoxia , aim2 , caspase 1 , inflammation , pyroptosis , cytokine , microbiology and biotechnology , signal transduction , biology , chemistry , immunology , cancer research , medicine , lung
The inflammasome is a newly discovered molecular platform required for the caspase‐1 activation and maturation of IL‐1β. IL‐1β is the most active cytokine in acute lung injury patients. Recently it has been reported that reactive oxygen species (ROS) are required for purinergic P2X7 receptor (P2X7R)‐mediated NALP3 inflammasome activation. Our previous results suggest that suppressor of cytokine signaling‐1 (SOCS‐1) functions as negative regulator in ROS‐induced apoptotic responses by inducing ASK‐1 degradation. Thus, we hypothesized that the toxic effects of hyperoxia could be mediated by ASK‐1‐induced P2X7 mediated inflammasome and that the protective effects of SOCS‐1 could be due, at least in part, to its ability to suppress inflammasome response. To test this hypothesis we administered SOCS–1 adenovirus (Ad‐SOCS‐1) into the lung and exposed mice to 100%O2. Ad‐GFP infected mice were used as controls. Inflammasome complex formation was assessed by immunoprecipitation and western blot. Ad‐SOCS‐1 mice lived significantly longer in hyperoxia when compared to Ad‐GFP. After 72 hours of hyperoxia, inflammasome was activated and associated with enhanced caspase‐1and IL‐1 β cleavage in the Ad‐GFP mice but inflammasome assembly was abolished in the Ad‐SOCS‐1 mice with significant decrease in caspase‐1and IL‐1 β cleavage. These findings suggest that SOCS‐1 over‐expressing mice are protected from hyperoxia‐induced inflammation, which is associated with inactivation of inflammasome, thus demonstrating a critical role for SOCS‐1 in inflammasome‐mediated inflammation. (This work was funded by T32‐ HL007874 ).