Protein arginine methyltransferase 5 mediates THP1derived macrophage activation dependent on NFκB in endometriosis

Macrophageinduced inflammation is a major factor in the pathogenesis of endometriosis. The underlying mechanisms, however, remain largely unknown. TNFα, IL6, IL10 and CC 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 transcriptionquantitative PCR and western blotting. IL6 and IP10 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 THP1derived 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 macrophagederived PRMT5 in mediating the interaction between macrophages and endometrium in endometriosis. Mechanistically, macrophage PRMT5 expression was regulated in an NFκBdependent and Smad2/3independent manner, indicating that PRMT5 is a downstream target of NFκB. Importantly, macrophagederived PRMT5 was required for macrophage activation in endometriosis, as evidenced by the PRMT5dependent secretion of IL6 and IFNγinduced protein 10 from THP1derived macrophages. The present study identified NFκBdependent PRMT5 as a novel regulator of macrophage activation in endometriosis. Targeting PRMT5 in macrophages may be a potential therapeutic strategy against endometriosis.