Figure 6.

Simplified diagram of the proposed signalling events leading to Cyp7b gene transcription in synovial fibroblasts. Using inhibitors of the mitogen-activated protein kinase (MAPK) kinase (MEK)1/extracellular signal (mitogenic)-regulated kinase (ERK)1/2 pathway (i.e. PD98059), the p38 MAPK pathway (i.e. SB203580), the c-Jun-NH₂-terminal kinase (JNK) pathway (i.e. SP600125), the IκB/nuclear factor-κB (NF-κB) pathway (i.e. PSI; dashed line) and the NF-κB/activator protein (AP)-1 pathway SN50, it was established that the NF-κB and AP-1 pathway is relevant to Cyp7b activity. All experiments were performed using synovial fibroblasts derived from patients with rheumatoid arthritis. Cyp7b, cytochrome p450 enzyme 7b; IκBα, inhibitor of NF-κB; IKK, IκB kinase complex (composed of three subunits – IKKα, IKKβ, and IKKγ [NEMO]; RelA (p65) and NF-κB1 [p50/p105] are subunits of NF-κB); RIP, receptor interacting protein; TNF, tumour necrosis factor; TNFR, TNF-α receptor; TRADD, TNF receptor associated death domain; TRAF, TNF receptor associated factor.