Inhibition of Toll-like receptor 9 attenuates sepsis-induced mortality through suppressing excessive inflammatory response

Dan Hu, Xiaohua Yang, Yanxiao Xiang, Hui Li, Hui Yan, Jun Zhou, Yi Caudle, Xiumei Zhang, Deling Yin

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)92-98
Number of pages7
JournalCellular Immunology
Volume295
Issue number2
DOIs
StatePublished - Jun 1 2015
Externally publishedYes

Keywords

  • Cytokines
  • Immune response
  • Sepsis
  • TLR9

ASJC Scopus subject areas

  • Immunology

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