In the synovial tissue of RA, p38 is activated and highly expressed by MKK3 and MKK6,207 and commonly used p38 MAPK inhibitors reduce the generation of pro-inflammatory cytokines in neutrophils, macrophages/monocytes, and T lymphocytes.203 P38 MAPK activates and moves into the nucleus, phosphorylating transcription factors such as ATF2, MEF2C,208,209 and these initiate cascades that induce a large increase in inflammatory chemokines like IL-8 and monocyte chemoattractant protein-1 (MCP-1), resulting in synovial thickening. The gene discussed is CXCL8; the disease is rheumatoid arthritis.