Hyperoxia induces inflammation and regulates cytokine production in alveolar epithelium through TLR2/4-NF-κB-dependent mechanism.
OBJECTIVE
It has been reported that inflammation of lung could be induced by proinflammatory factor under hyperoxia, which may be attributed by increasing generation of reactive oxygen species (ROS).


METHODS
In the present study, with human epithelial lung cancer cell line A549 treated with hyperoxia as in vitro model, we found that hyperoxia stimulation induced TLR2/4 activity in A549 cells. ROS inhibitor NAC was used to investigate the role of ROS in hyperoxia-induced inflammatory cytokines secretion.


RESULTS
Results of mRNA to protein level showed that elevated TLR2/4 activity and hyperoxia-induced inflammatory cytokines secretion could be significantly attenuated by NAC. EMSA results showed the activation of nuclear factor-κB (NF-κB) increased after 2-h hyperoxia stimulation, and the ROS inhibitor blocked TLR2/4 and NF-κB activity.


CONCLUSIONS
Data suggested that the TLR2/4-NF-κB pathway is involved in hyperoxia-induced inflammatory cytokines secretion in A549 human type II alveolar epithelial cells.
Department of Pediatric Intensive Care Unit, Guizhou Provincial People's Hospital, GuiYang, China. xu_fengmail@163.com.
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D000111:Acetylcysteine / Q000494:pharmacology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000032:analysis / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D018496:Hyperoxia; D007249:Inflammation; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
D016207:Cytokines; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D000111:Acetylcysteine