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Τετάρτη 4 Αυγούστου 2021

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

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Exp Ther Med. 2021 Sep;22(3):1003. doi: 10.3892/etm.2021.10436. Epub 2021 Jul 15.

ABSTRACT

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.

PMID:34345285 | PMC:PMC8311241 | DOI:10.3892/etm.2021.10436

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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