[No authors listed]
Sepsis is characterized by systemic inflammatory responses. In the present study, the role of deleted in liver cancer 1 (DILC), interleukin (IL)â6, signal transducer and activator of transcription 3 and Tollâlike receptor 4 (TLR4) in the pathogenesis of sepsis was investigated. Reverse transcriptionâquantitative polymerase chain reaction analysis and western blotting were performed to evaluate the effects of lipopolysaccharide (LPS) on the expression of DILC, ILâ6, and TLR4, in addition to the effects of DILC and ILâ6 on the synthesis of tumor necrosis factor (TNFâα), chemokine ligand 5 (CCL5), Eâselectin and CâXâC motif chemokine receptor 1 (CXCR1). In addition, the regulatory association between DILC, ILâ6, and TLR4 was investigated. LPS reduced the expression level of DILC, and enhanced the expression of ILâ6, duanyu18133 and TLR4. DILC directly and negatively regulated the synthesis of ILâ6, as demonstrated by the markedly decreased luciferase activity in cells transfected with a wildâtype DILC plasmid. On the other hand, compared with the scramble control, DILC and ILâ6 small interfering (si)RNAs significantly suppressed the expression of ILâ6, duanyu18133 and TLR4. In addition, DILC siRNA enhanced the expression of ILâ6, duanyu18133 and TLR4, whereas the expression levels of TNFâα, CCL5, Eâselectin and CXCR1 in LPSâtreated THPâ1 cells were downregulated following transfection with DILC and ILâ6 siRNAs. In patients with sepsis, DILC expression was inhibited, although the expression levels of ILâ6, duanyu18133 and TLR4 were upregulated. In addition, the expression levels of TNFâα, CCL5, Eâselectin and CXCR1 in patients with sepsis were higher compared with normal subjects. Therefore, DILC may mediate the crosstalk between the cascades of and TNFâα signaling, indicating that DILC may act as a prognostic biomarker of sepsis, and may serve as a potential therapeutic target for the treatment of sepsis.
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