LncRNA-Cox2 has been reported to regulate macrophage polarization, and the activation of macrophages is a major participant in the pathogenesis of sepsis. Therefore, we explored whether lncRNA-Cox2 was involved in the progression of sepsis. In this study, we established a cecal ligation and puncture (CLP) mouse model and found that silencing lncRNA-Cox2 in CLP mice improved the 7-day survival rate, and alleviated the increase of blood bacterial burdens, systemic inflammatory response, and pulmonary dysfunction induced by CLP. Besides, interference with lncRNA-Cox2 declined the percentage of M1 macrophages and increased the percentage of M2 macrophages in the spleens of CLP mice. In vitro, the knockdown of lncRNA-Cox2 suppressed LPS-induced inflammation and M1 macrophage marker expression, and promoted M2 macrophage marker expression in primary peritoneal macrophages and RAW264.7 cells. Moreover, lncRNA-Cox2 induced CREB phosphorylation by binding to CREB, and increased phosphorylated-CREB enrichment in the C/EBPβ promoter region, so as to promote C/EBPβ transcription, thereby activating the CREB-C/EBPβ cascade. In addition, overexpressing lncRNA-Cox2 enhanced the effect of LPS on inflammation and macrophage polarization, which was reversed by treatment with 666-15 (an inhibitor of CREB). In conclusion, silencing lncRNA-Cox2 restrained the progression of sepsis in mice by modulating macrophage polarization and inflammatory response through suppressing CREB-C/EBPβ pathway.
Keywords: CREB-C/EBPβ pathway; Inflammation; LncRNA-Cox2; Macrophage polarization; Sepsis.
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