In our studies, we found that Cyr61 enhanced AP-1, C/EBPβ and NF-κB binding to the IL-8 promoter simultaneously, suggesting that signaling pathways mediated by Cyr61 provoke an interaction among these transcription factors and may contribute to the formation of an enhanceosome-like structure for IL-8 production in RA FLS, even though the p38 MAPK pathway was not active in Cyr61-induced IL-8 production in RA FLS. Here, CXCL8 is linked to rheumatoid arthritis.