Arthrospira platensis polysaccharide alleviates inflammation induced by PRV in RAW264.7 cells and mice via the regulation of LncRNA Dhx35/mmu-miR-185-3p/IL-17RA

Abstract

Pseudorabies virus (PRV) poses a great danger to pig farming and human public health safety. Previous studies have shown that the first component of Arthrospira platensis polysaccharide (PAP-1) may alleviate the inflammatory response of RAW264.7 cells induced by PRV infection through the IL-17RA signaling pathway and its circRNA-miRNA-mRNA network, but the specific mechanism is not clear. In this study, we screened the LncRNA sequences related to IL-17RA signaling pathway by transcriptomics data. The mechanism was verified by gene interference or overexpression and dual luciferase experiments to investigate the regulatory mechanism of PAP-1 on IL-17RA inflammatory signaling pathway in PRV infection. In vitro studies showed that PAP-1 significantly reduced the PRV-induced elevated expression of IL-17RA signaling pathway inflammatory factors such as IL-17RA, IL-1β, CXCL10, and iNOS in RAW264.7 cells (P < 0.05). On this basis, the key regulatory factor LncRNA Dhx35 of IL-17 RA signaling pathway was screened by whole transcriptome sequencing analysis. It was found that PAP-1 could reduce the transcriptional activity of IL-17RA by down-regulating PRV-induced LncRNA Dhx35 as a competing endogenous RNA to bind to mmu-miR-185-3p, which decreased the inflammatory response. In vivo experiments revealed that PAP-1 down-regulated the expression of LncRNA Dhx35, up-regulated the expression of mmu-miR-185-3p, and significantly down-regulated the expression of IL-17RA, IL-1β, CXCL10, and iNOS in lung tissues of PRV-infected mice (P < 0.05). Taken together, our data suggest that PAP-1 reduces PRV infection-induced inflammatory responses in RAW264.7 cells and mouse lung tissues by regulating LncRNA Dhx35/mmu-miR-185-3p/IL-17RA.