Inhibition of Toll-Like Receptor 9 Attenuates Sepsis-Induced Mortality Through Suppressing Excessive Inflammatory Response
Document Type
Article
Publication Date
6-1-2015
Description
Sepsis, a major clinical problem with high morbidity and mortality, is caused by overwhelming systemic host-inflammatory response. Toll-like receptors (TLRs) play a fundamental role in induction of hyperinflammation and tissue damage in sepsis. In this study, we demonstrate a protective role of TLR9 inhibition against the dysregulated inflammatory response and tissue injury in sepsis. TLR9 deficiency decreased the mortality of mice following cecal ligation and puncture (CLP)-induced sepsis. TLR9 knockout mice showed dampened p38 activation and augmented Akt phosphorylation in the spleen, lung and liver. In addition, TLR9 deficiency decreased the levels of inflammatory cytokines and attenuated splenic apoptosis after CLP. These results indicate that TLR9 inhibition might offer a novel therapeutic strategy for the management of sepsis.
Citation Information
Hu, Dan; Yang, Xiaohua; Xiang, Yanxiao; Li, Hui; Yan, Hui; Zhou, Jun; Caudle, Yi; Zhang, Xiumei; and Yin, Deling. 2015. Inhibition of Toll-Like Receptor 9 Attenuates Sepsis-Induced Mortality Through Suppressing Excessive Inflammatory Response. Cellular Immunology. Vol.295(2). 92-98. https://doi.org/10.1016/j.cellimm.2015.03.009 PMID: 25880099 ISSN: 0008-8749