Long non‑coding RNA DILC is involved in sepsis by modulating the signaling pathway of the interleukin‑6/signal transducer and activator of transcription 3/Toll‑like receptor 4 axis.

Abstract

Sepsis is characterized by systemic inflammatory responses. In the present study, the role of deleted in liver cancer 1 (DILC), interleukin (IL)‑6, signal transducer and activator of transcription 3 (STAT3), and Toll‑like receptor 4 (TLR4) in the pathogenesis of sepsis was investigated. Reverse transcription‑quantitative polymerase chain reaction analysis and western blotting were performed to evaluate the effects of lipopolysaccharide (LPS) on the expression of DILC, IL‑6, STAT3, and TLR4, in addition to the effects of DILC and IL‑6 on the synthesis of tumor necrosis factor (TNF‑α), chemokine ligand 5 (CCL5), E‑selectin and C‑X‑C motif chemokine receptor 1 (CXCR1). In addition, the regulatory association between DILC, IL‑6, STAT3 and TLR4 was investigated. LPS reduced the expression level of DILC, and enhanced the expression of IL‑6, STAT3 and TLR4. DILC directly and negatively regulated the synthesis of IL‑6, as demonstrated by the markedly decreased luciferase activity in cells transfected with a wild‑type DILC plasmid. On the other hand, compared with the scramble control, DILC and IL‑6 small interfering (si)RNAs significantly suppressed the expression of IL‑6, STAT3 and TLR4. In addition, DILC siRNA enhanced the expression of IL‑6, STAT3 and TLR4, whereas the expression levels of TNF‑α, CCL5, E‑selectin and CXCR1 in LPS‑treated THP‑1 cells were downregulated following transfection with DILC and IL‑6 siRNAs. In patients with sepsis, DILC expression was inhibited, although the expression levels of IL‑6, STAT3 and TLR4 were upregulated. In addition, the expression levels of TNF‑α, CCL5, E‑selectin and CXCR1 in patients with sepsis were higher compared with normal subjects. Therefore, DILC may mediate the crosstalk between the cascades of IL‑6/STAT3 and TNF‑α 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.

• Authors: Weiping Huang, Linqiang Huang, Miaoyun Wen, Ming Fang, Yiyu Deng, Hongke Zeng
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 18 Issue 6 Pg. 5775-5783 (Dec 2018) ISSN: 1791-3004 [Electronic] Greece
• PMID: 30365067 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Cytokines
• Inflammation Mediators
• Interleukin-6
• Lipopolysaccharides
• RNA, Long Noncoding
• STAT3 Transcription Factor
• Toll-Like Receptor 4

Topics

• Biomarkers
• Case-Control Studies
• Cytokines (genetics, metabolism)
• Gene Expression Regulation
• Humans
• Inflammation Mediators (metabolism)
• Interleukin-6 (genetics, metabolism)
• Lipopolysaccharides (adverse effects)
• RNA Interference
• RNA, Long Noncoding (genetics)
• STAT3 Transcription Factor (metabolism)
• Sepsis (diagnosis, etiology, metabolism)
• Signal Transduction
• Toll-Like Receptor 4 (metabolism)