Polyene phosphatidylcholine ameliorates synovial inflammation: involvement of PTEN elevation and glycolysis suppression

Background: Synovial inflammation, characterized by the activation of synovial fibroblasts (SFs), is a crucial factor to drive the progression of rheumatoid arthritis (RA). Polyene phosphatidylcholine (PPC), the classic hepatoprotective drug, has been reported to ameliorate arthritis in Animals. However, the molecular mechanism remains poorly understood. METHODS AND RESULTS: Using in vitro primary synovial fibroblast (SFs) culture system, we revealed that Phosphatase and tension homolog deleted on chromosome 10 (PTEN), a tumor suppressor, mediates the anti-inflammatory effect of PPC in lipopolysaccharide (LPS)-stimulated primary SFs. PPC decreased the production of TNF-α and IL-6 production while elevating the level of IL-10 and TGF-β. Furthermore, PPC up-regulated the expression of PTEN, but inhibited the expression of p-AKT (ser473) and PI3K-p85α. Moreover, pre-treatment of SF1670 (the inhibitor of PTEN) or 740Y-P (the agonist of Akt/PI3K pathways) partially abrogated the anti-inflammatory effect of PPC. In addition, PPC could inhibit the expression of GLUT4, a key transporter of glucose that fuels the glycolysis, which is accompanied by the expression downregualtion of glycolytic Enzymes PFKFB3 and PKM2. Furthermore, PPC could reduce ROS production and mitochondrial membrane potential in LPS-stimulated SFs and MH7A cell line.

Conclusion: The present study supported that PPC can alleviate synovial inflammation, which involves in the elevation of PTEN and blockage of glycolysis.

Glycolysis; PTEN; Polyene phosphatidylcholine; Rheumatoid athritis; Synovial inflammation.