title: The effects of Twist-2 on liver endotoxin tolerance induced by a low dose of lipopolysaccharide.
abstract: Endotoxin tolerance is an important mechanism for preventing uncontrolled inflammatory cytokine production in bacterial sepsis. However, its molecular mechanisms remain largely unknown. It was reported that Twist-2 protein was a negative regulator for cytokine signaling by repressing the nuclear factor (NF)-κB-dependent cytokine pathway. However, the relationship between Twist-2 and endotoxin tolerance is unclear. Endotoxin tolerance models of BABL/c mice and isolated Kupffer cells (KCs) were established to observe the changes of Twist-2 during endotoxin tolerance. Then, Twist-2 shRNA was used to specifically inhibit Twist-2 gene in KCs to further explore the role of Twist-2 in endotoxin tolerance. The expression of Twist-2 was analyzed by immunohistochemistry, reverse transcription polymerase chain reaction, and Western blotting, respectively. The responses to lipopolysaccharide were assessed by the activation of nuclear factor-κB and the production of tumor necrosis factor-α. The histopathologic changes in the liver of the non-endotoxin tolerance group were more serious than those of the endotoxin tolerance group. Endotoxin tolerance also led to less activation of nuclear factor-κB, lower expression levels of tumor necrosis factor-α mRNA, and more expression of Twist-2 than those of non-endotoxin tolerance group in liver and KCs. Moreover, the inhibitive effects partly weaken in KCs transfected with Twist-2 shRNA. Twist-2 was involved in endotoxin tolerance through inhibiting NF-κB trans-activation and cytokines transcriptional activities. It may be a new target for the clinical treatment of sepsis and other inflammatory diseases.
authors.affiliation: Chongqing Key Laboratory of Hepatobiliary Surgery and Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, People's Republic of China.
authors.forename: Peizhi
authors.initials: P
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Kun
authors.initials: K
authors.lastname: He
authors.forename: Kaichan
authors.initials: K
authors.lastname: Zhong
authors.forename: Jianping
authors.initials: J
authors.lastname: Gong
authors.forename: Haibo
authors.initials: H
authors.lastname: You
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D007108:Immune Tolerance / Q000235:genetics / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D007728:Kupffer Cells / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008099:Liver / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D018805:Sepsis / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D051996:Transcription Factor RelA / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D051879:Twist-Related Protein 1 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
chemical_list: D008070:Lipopolysaccharides; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C498144:Rela protein, mouse; D012097:Repressor Proteins; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D051879:Twist-Related Protein 1; C096852:Twist2 protein, mouse