Activation of TLR4-mediated NFkappaB signaling in hemorrhagic brain in rats.
Inflammation and immunity play a crucial role in the pathogenesis of Intracerebral hemorrhage (ICH). Toll-like receptor 4- (TLR4-) mediated nuclear factor kappa-B (NFkappaB) signaling plays critical roles in the activation and regulation of inflammatory responses in injured brain. However, the involvement of TLR4-mediated NFkappaB signaling in the pathogenesis of ICH remains unknown. The present study was to evaluate the temporal profile of the expression of TLR4 and the activation of TLR4-mediated NFkappaB signaling in brain tissues of Wistar rats after ICH. TLR4 mRNA and protein, the phosphorylation of inhibitors of kappa B (p-IkappaBalpha), and the activity of NFkappaB were examined in hemorrhagic cerebral tissue by Rt-PCR, Western blots, immunohistochemistry staining, and EMSA. Compared with saline control, the TLR4 mRNA and protein significantly increased starting at 6 hours after ICH, peaked on the 3rd day after ICH, and then decreased but still maintained at a higher level on the 7th day after ICH (P < .05). The level of p-IkappaBalpha and the activity of NFkappaB also increased in the brain after ICH compared with saline control. The present study firstly suggests that TLR4-mediated NFkappaB signaling participates in the pathogenesis of ICH, which may become a therapeutic target for ICH-induced brain damage.
Department of Neurology, The First Affiliated Hospital, China Medical University, Shenyang 110001, China. tengweiyucmu@126.com
Weiyu
W
Teng
Lishu
L
Wang
Weishuang
W
Xue
Chao
C
Guan
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002543:Cerebral Hemorrhage / Q000378:metabolism; D005786:Gene Expression Regulation; D020672:I-kappa B Proteins / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606206:Nfkbia protein, rat; D012333:RNA, Messenger; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D000072000:NF-KappaB Inhibitor alpha