Epigenetic regulation by oleacein mitigates IL-1β-induced inflammation in human SW982 synovial cells

Abstract

Inflammatory arthritis is a term used to describe a diverse group of rheumatic disorders involving the inflammation and hyperproliferation of synovial joints and systemic manifestations. Oleacein (OLA) is one of the most abundant secoiridoids in extra virgin olive oil, the principal source of fat in the Mediterranean diet, which has been shown to exhibit beneficial effects. The objective of the study was to explore the antioxidant and anti-inflammatory effects induced by OLA in a human cell line of synovial cells (SW982), as well as to evaluate its possible role as an epigenetic modulator through the regulation of DNA methylation. Sulforhodamine B assay was utilised to assess cell viability. The levels of inflammatory marker production (MMP-1, MMP-3, TNF-α, IL-1β, IL-6, and PGE2) were evaluated by ELISA, and IL-8 gene expression was analysed by RT-qPCR. The expression of pro-inflammatory enzymes, including COX-2 and mPGES-1, and signaling pathways (MAPK, NF-κB, Keap1/Nrf-2/HO-1 and inflammasome) were evaluated by western blotting. In addition, global DNA methylation was analysed by ELISA, and we studied the gene expression of DNMT1/3A enzymes by RT-qPCR. OLA exhibited anti-inflammatory and antioxidant effects through the regulation of key inflammatory signaling pathways such as inflammasome, MAPK, NF-κB, and the Keap1/Nrf-2/HO-1 axis. In addition, it reduced the production and expression of pro-inflammatory markers (COX-2, mPGES-1, MMP-1, MMP-3, IL-8, IL-6, TNF-α and PGE₂) and regulated IL-1β-induced changes in DNA methylation modulating DNMT1 and DNMT3 gene expression and global DNA methylation. These results show OLA as a promising epigenetic regulator of the inflammatory response in rheumatic diseases.