Co-culture of macrophage supernatants generated from stimulation with MAA- and citrullinated fibrinogen (FIB-MAA-CIT) with RA derived HFLS led to an aggressive fibroblast phenotype characterized by increased ECM secretion (vs. supernatants generated from FIB-MAA or FIB-CIT); mediated in part by PDGF-BB secretion from macrophages and JNK, Erk1/2, and Akt signaling in HFLS. This evidence concerns the gene MAPK8 and rheumatoid arthritis.