Protein arginine methyltransferase 5 mediates THP-1-derived macrophage activation dependent on NF-κB in endometriosis

Macrophage-induced inflammation is a major factor in the pathogenesis of Endometriosis. The underlying mechanisms, however, remain largely unknown. TNF-α, IL-6, IL-10 and C-C motif chemokine 20 (CCL20) levels in endometrial extracts were determined using Luminex cytokine kits. Additionally, protein arginine methyltransferase 5 (PRMT5) levels were measured using reverse transcription-quantitative PCR and western blotting. IL-6 and IP-10 levels in cells were measured using ELISA kits. In the present study, it was revealed that PRMT5 expression at both the mRNA and protein levels in THP-1-derived Macrophages was significantly decreased following treatment with serum or extracts of endometrium from patients with Endometriosis in the presence of lipopolysaccharide, compared with that in control cells, suggesting a possible role for macrophage-derived PRMT5 in mediating the interaction between Macrophages and endometrium in Endometriosis. Mechanistically, macrophage PRMT5 expression was regulated in an NF-κB-dependent and SMAD2/3-independent manner, indicating that PRMT5 is a downstream target of NF-κB. Importantly, macrophage-derived PRMT5 was required for macrophage activation in Endometriosis, as evidenced by the PRMT5-dependent secretion of IL-6 and IFN-γ-induced protein 10 from THP-1-derived Macrophages. The present study identified NF-κB-dependent PRMT5 as a novel regulator of macrophage activation in Endometriosis. Targeting PRMT5 in Macrophages may be a potential therapeutic strategy against Endometriosis.