Silencing of LncRNA-PVT1 ameliorates lipopolysaccharide-induced inflammation in THP-1-derived macrophages via inhibition of the p38 MAPK signaling pathway

Background: Sepsis is common in intensive care units and has a high mortality rate; yet, its pathogenesis and treatment remain unclear. Recent studies have shown that long non-coding RNA plasmacytoma variant translocation 1 (lncRNA-PVT1) plays a pro-inflammatory role in immune-related inflammatory diseases. Therefore, we investigated whether lncRNA-PVT1 plays an important pro-inflammatory effect in the inflammatory response of sepsis. Methods: Quantitative real-time PCR (RT-qPCR) was employed for the detection of lncRNA-PVT1, interleukin 113 (IL-113), and tumor necrosis factor alpha (TNF-alpha) mRNA, and the correlations between their expressions were analyzed. After lncRNA-PVT1 knockdown by lncRNA Smart Silencer, abnormal expressions of lncRNA-PVT1, and IL-113 and TNF-alpha mRNA were detected. The expressions of total and phosphorylated protein of p38 were detected by western blotting. The effect of silencing lncRNA-PVT1 on p38 mitogen-activated protein kinase (MAPK) signaling pathway during lipopolysaccharide (LPS)induced inflammation was subsequently analyzed. The MAPK selective inhibitor, SB202190, was used to block this signaling pathway, and the expressions of lncRNA-PVT1 and TNF-alpha were detected by RT-qPCR. Furthermore, the effect of partial blockade of the p38 MAPK signaling pathway by SB202190 on the levels of lncRNA-PVT1 was explored. Results: Following treatment of THP-1-derived macrophages with different concentrations of LPS, the levels of lncRNA-PVT1 and IL-113, TNF-alpha mRNA were increased in a dose-dependent manner. Silencing of lncRNA-PVT1 reduced the expressions of IL-113 and TNF-alpha mRNA via inhibition of the p38 MAPK signaling pathway. Specifically, inhibiting the p38 MAPK pathway significantly decreased the LPS-induced lncRNA-PVT1 elevation. Conclusions: Our observations suggest that lncRNA-PVT1 can be silenced to ameliorate LPS-induced inflammation in macrophages via inhibition of the p38 MAPK pathway. Further, the p38 MAPK pathway can regulate the expression of lncRNA-PVT1 via a positive feedback loop.

Automated summary

The study demonstrated that lncRNA-PVT1 plays a crucial role in the inflammatory response of sepsis through the p38 MAPK signaling pathway, and it can regulate its own expression through a positive feedback loop, providing a potential therapeutic target for LPS-induced inflammation.