A schematic model for Cyr61-stimulated IL-8 production and its role in the migration of neutrophils. Cyr61 secreted by FLS stimulates IL-8 production via AKT, JNK and ERK1/2-dependent AP-1, C/EBP and NF-κB signaling pathways. Production of IL-8 recruits an abundance of neutrophils to the site of inflammation. In turn, neutrophils are able to release cytotoxic mediators, cytokines and chemokines into the diseased joints, leading to tissue damage and cartilage destruction. Thus, Cyr61 might act as a novel proinflammatory factor contributing to the inflammation of RA via stimulation of neutrophil migration. FLS, fibroblast-like synoviocytes; RA, rheumatoid arthritis.