Figure 9.

A schematic model of signaling pathways involved in MIF-induced MMP-2 expression in rheumatoid arthritis (RA) synovial fibroblasts. Upregulation of MMP-2 by MIF involves JNK, PKCδ, and Src activation. Activation of JNK and PKCδ by MIF requires Src. Phosphorylation of PKCδ occurs through Src and JNK signaling intermediates. Phosphorylation of PKCδ and JNK leads to the activation and nuclear translocation of c-jun JNK, c-jun N-terminal kinase; MIF, macrophage migration inhibitory factor; MMP, matrix metalloproteinase; P, phosphorylation; PKC, protein kinase C.