CCN1 and rheumatoid arthritis: In synovial fibroblasts from human RA patients, protein I/II and uric acid, a pathogen-associated molecular pattern from oral streptococci and a major component secreted from necrotic cells, respectively, have been demonstrated to stimulate IL-8 production and secretion via ERK1/2 and JNK [53, 54] Cyr61/CCN1, a product of an immediate early gene with roles in the mediation of cell adhesion and induction of cell migration, also stimulated IL-8 expression via ERK1/2 and JNK activation in RA synovial fibroblasts [55].