title: Lrg participates in lipopolysaccharide preconditioning-induced brain ischemia injury via TLR4 signaling pathway.
abstract: Lipopolysaccharide (LPS) preconditioning is a powerful neuroprotective phenomenon by which an injurious stimulus renders the brain resistant to a subsequent damaging ischemic insult. The LPS response gene (Lrg) is a recently identified gene in human dental pulp cells treated with LPS. However, the role and mechanism of Lrg in brain ischemia injury have not yet been demonstrated. Here, we sought to determine whether Lrg participates in LPS preconditioning-induced brain ischemia injury. The Lrg protein accumulates in brain tissue after middle cerebral artery occlusion (MCAO). Furthermore, knockdown of Lrg by small interfering RNA (siRNA) significantly increased the infarct size of brain injury. In addition, we investigated the mechanism of Lrg in brain ischemia injury. Lrg-siRNA could regulate inflammatory cytokine expression. Moreover, interleukin-1 receptor-associated kinase 1 (IRAK-1) and nuclear factor Kappa B (NF-κB) p65 protein levels were significantly increased by Lrg-siRNA in mice after MCAO. Conversely, interferon regulatory factor 3 (IRF3) protein level was decreased by Lrg-siRNA. Taken together, these results suggest that Lrg regulates the expression of inflammatory cytokines in LPS preconditioning-induced brain ischemia injury via the toll-like receptor 4 (TLR4) signaling pathway. Lrg may therefore serve as a novel therapeutic target for brain ischemia injury.
authors: Department of Anesthesia, General Hospital of Chengdu Military Area Command, Chengdu, 610000, Sichuan, China.
authors: Gu
authors: G
authors: Gong
authors: Shurong
authors: S
authors: Bai
authors: Wei
authors: W
authors: Wu
authors: Ling
authors: L
authors: Hu
authors: Yinghai
authors: Y
authors: Liu
authors: Jie
authors: J
authors: Niu
authors: Xuemei
authors: X
authors: Dai
authors: Liang
authors: L
authors: Yin
authors: Xiaowu
authors: X
authors: Wang
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism*; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000378:metabolism; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; C530631:LRG1 protein, mouse; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; D053592:Interleukin-1 Receptor-Associated Kinases; C507769:Irak1 protein, mouse