title: 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.
authors.affiliation: Department of Internal Medicine, College of Medicine, East Tennessee State University, Johnson City, TN, USA; Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of Internal Medicine, College of Medicine, East Tennessee State University, Johnson City, TN, USA.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Internal Medicine, College of Medicine, East Tennessee State University, Johnson City, TN, USA; Department of Pharmacology, Shandong University School of Medicine, Jinan, China.
authors.forename: Yanxiao
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Department of Internal Medicine, College of Medicine, East Tennessee State University, Johnson City, TN, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Internal Medicine, College of Medicine, East Tennessee State University, Johnson City, TN, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Radiology,Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Internal Medicine, College of Medicine, East Tennessee State University, Johnson City, TN, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Caudle
authors.affiliation: Department of Pharmacology, Shandong University School of Medicine, Jinan, China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine, College of Medicine, East Tennessee State University, Johnson City, TN, USA. Electronic address: yin@etsu.edu.
authors.forename: Deling
authors.initials: D
authors.lastname: Yin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D020287:In Situ Nick-End Labeling; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000276:immunology; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D051058:Oncogene Protein v-akt / Q000276:immunology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018805:Sepsis / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology
chemical_list: D016207:Cytokines; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D012313:RNA; D051058:Oncogene Protein v-akt; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Cytokines; Immune response; Sepsis; TLR9