HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

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

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.
AuthorsDan Hu, Xiaohua Yang, Yanxiao Xiang, Hui Li, Hui Yan, Jun Zhou, Yi Caudle, Xiumei Zhang, Deling Yin
JournalCellular immunology (Cell Immunol) Vol. 295 Issue 2 Pg. 92-8 (Jun 2015) ISSN: 1090-2163 [Electronic] Netherlands
PMID25880099 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier Inc. All rights reserved.
Chemical References
  • Cytokines
  • Tlr9 protein, mouse
  • Toll-Like Receptor 9
  • RNA
  • Oncogene Protein v-akt
  • p38 Mitogen-Activated Protein Kinases
Topics
  • Animals
  • Apoptosis (immunology)
  • Cytokines (genetics, immunology)
  • In Situ Nick-End Labeling
  • Kaplan-Meier Estimate
  • Liver (immunology)
  • Lung (immunology)
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Oncogene Protein v-akt (immunology)
  • RNA (chemistry, genetics)
  • Real-Time Polymerase Chain Reaction
  • Sepsis (immunology, pathology)
  • Spleen (immunology)
  • Toll-Like Receptor 9 (antagonists & inhibitors, genetics, immunology)
  • p38 Mitogen-Activated Protein Kinases (immunology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: