Simplified diagram of the proposed signalling events leading to Cyp7b gene transcription in synovial fibroblasts

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.

Publication

Tumour necrosis factor-α stimulates dehydroepiandrosterone metabolism in human fibroblast-like synoviocytes: a role for nuclear factor-κB and activator protein-1 in the regulation of expression of cytochrome p450 enzyme 7b. (2005) John Dulos, et al. Arthritis Res Ther. 2005;7(6):R1271-R1280. Figure: F6. All organisms Mus musculus Homo sapiens Bos taurus Capra hircus Arabidopsis thaliana

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