title: Role of Toll-Like Receptor 3 in Lung Ischemia-Reperfusion Injury.
abstract: Lung ischemia-reperfusion injury (LIRI) occurs in various clinical situations, such as transplantation, cardio pulmonary bypass, cardiac arrest, and major trauma, leading to significant morbidity and mortality. Despite researchers having spent years of effort to investigate the pathogenesis of pulmonary ischemic injury, the concrete cellular and molecular mechanisms are still unknown. We hypothesized that toll-like receptor (TLR) 3 signaling may play a vital role in inflammation responses, apoptosis, and pulmonary dysfunction during LIRI. Lung ischemia-reperfusion (I/R) mouse model was established by the occlusion of the left pulmonary hilum of adult male C57BL/6J wild-type (WT) and TLR3 deficient (TLR3) mice for 1 h, followed by reperfusion for 2 h. Blood serum and lung tissues of the mice were collected after lung I/R for subsequent experiments. Compared with WT mice, TLR3 mice had better preserved pulmonary function, and significantly attenuated pulmonary cytokines mRNA and protein production after I/R. Pulmonary apoptosis was also inhibited after TLR3 knockout, as indicated by cleaved caspase-3 western blot and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Levels of serum microRNAs (miRNAs), especially miRNA155, were decreased in the TLR3 I/R group compared with that of the WT I/R group. In conclusion, these data suggest that TLR3 signaling pathway may be a promising target for the treatment of lung I/R injury.
authors.affiliation: Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
authors.forename: Xi-Yang
authors.initials: XY
authors.lastname: Zhang
authors.forename: Chan
authors.initials: C
authors.lastname: Chen
authors.forename: Ya-Bing
authors.initials: YB
authors.lastname: Zhang
authors.forename: Si-Yang
authors.initials: SY
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Zhu
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.forename: Gang
authors.initials: G
authors.lastname: Ma
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D008168:Lung / Q000378:metabolism; D008171:Lung Diseases / Q000097:blood / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000097:blood; D015427:Reperfusion Injury / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D035683:MicroRNAs; D051196:Toll-Like Receptor 3; D053148:Caspase 3