Activation of TLR4-mediated NFkappaB Signaling in Hemorrhagic Brain in Rats

Overview

Journal Mediators Inflamm

Publisher Wiley

Specialties Biochemistry
Pathology

Date 2010 Feb 13

PMID 20150961

Citations 41

Authors

Weiyu Teng

Lishu Wang

Weishuang Xue

Chao Guan

Affiliations

Soon will be listed here.

Abstract

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.

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