Abstract
Inflammatory and invasive fibroblast-like synoviocytes (FLS) contribute to the pathology of rheumatoid arthritis (RA). Isoginkgetin (IGKG) has been identified as having anti-inflammatory properties. This study investigated whether IGKG could be utilized to treat RA. Primary FLS were isolated from synovial tissues derived from six RA patients, which were over-expressed with matrix metallopeptidase 9 and cultured with or without tumor necrosis factor (TNF)-α and then further treated with IGKG. IGKG down-regulated the content of various interleukins (ILs), namely, IL-1β, IL-6, and IL-8, in RA-FLS supernatant with or without TNF-α stimulation, with diminished migration and invasion properties as assayed by the transwell system. Furthermore, down-regulated inflammatory cytokine secretion and down-regulated migration and invasion properties could be reversed through matrix metallopeptidase 9 overexpression. Dual-luciferase reporter gene assay indicated that IGKG could inhibit nuclear factor kappa B transcription activity. Western blot analysis also demonstrated that IGKG down-regulated the expression of p-IκBα, p-p65, and MMP9. IGKG displayed the ability to inhibit the inflammatory response of RA-FLS through the NF-κB/MMP9 pathway with diminished migration and invasion.