[Regulatory Effect of All-Trans Retinoic Acid on the Expression of IL-1ß in Macrophages and the Mechanisms Involved].

ABSTRACT

Objective: To investigate the regulatory effect of all-trans retinoic acid (ATRA) on the expression interleukin-1ß (IL-1ß) in macrophages and the mechanisms involved. Methods: Macrophages were treated with 1 µmol/L ATRA for 24 h before RNA-Sequence. Differentially expressed genes (DEGs) were screened out and analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, gene ontology (GO) functional analysis, and protein-protein interaction networks (PPI) analysis. After treatment with different doses of ATRA for 24 h, the expression of IL-1ß was examined with qRT-PCR and Western blot. The activation of NF-κB signaling and caspase-1 was observed by Western blot and immunofluorescence staining. Results: Compared with the blank control group, a total of 71 DEGs of macrophages were upregulated in the ATRA treatment group. KEGG analysis showed that the up-regulated DEGs were involved in IL-17 signaling pathway, tumor necrosis factor (TNF) signaling pathway, etc. GO analysis indicated that the up-regulated DEGs were involved in the biological processes of the production of IL-1ß, response to lipopolysaccharide, etc. PPI analysis revealed that inflammatory cytokines, adhesion molecules, and chemokines were the key genes that ATRA acted on. In vitro experiments showed that ATRA promoted IL-1ß expression in macrophages in a concentration-dependent manner. The expression of p-NF-κB, NF-κB, and caspase-1 were significantly increased by ATRA compared with those of the control group ( P<0.05), and p-NF-κB translocated to the cell nucleus in the ATRA group. Conclusion: ATRA may promote the expression of IL-1ß by activating NF-κB signaling and caspase-1 in macrophages, this study may provide evidence for the immune regulatory function of ATRA on macrophages.