Ginkgolide J protects human synovial cells SW982 via suppression of p38-dependent production of pro-inflammatory mediators

Fibroblast-like synoviocytes (FLS) in the synovial lining play a key role in the pathological process of rheumatoid arthritis (RA), which produce pro-inflammatory mediators to perpetuate inflammation and proteases to contribute to cartilage destruction. Ginkgolide J (GJ) is a subclass of ginkgolides (GGs) that exhibits anti-inflammatory activity. In the present study, the protective effect of GJ on lipopolysaccharide (LPS)-treated human synovial cells SW982 and its related mechanisms were investigated using various methods, including ELISA, Griess assay, western blotting, immunofluorescence analysis and p38 kinase activity assay. The results revealed that GJ pretreatment significantly attenuated LPS-induced excess production of pro-inflammatory mediators in SW982 cells via suppression of tumor necrosis factor-α/interleukin (IL)-1β/IL-18/NF-κB/NLR family pyrin domain containing 3, prostaglandin E2/cyclooxygenase-2 and inducible nitric oxide synthase/nitric oxide signaling. Mechanistic studies revealed that p38 activation contributed to the LPS-induced inflammatory response, and GJ pretreatment dose-dependently attenuated p38 activation, indicating that the suppressive effect of GJ was achieved by targeting p38 signaling. These findings may contribute to the prevention and treatment of RA.