c-Jun N-terminal kinase role in rheumatoid arthritis

Rheumatoid arthritis is a chronic inflammation characterized by cytokine production, synovial lining hyperplasia and joint destruction. The c-Jun N-terminal kinase (JNK) — a member of the mitogen-activated protein kinase family — is highly activated in rheumatoid arthritis fibroblast-like synoviocytes and synovium but its precise function remains unknown. In July Journal of Clinical Investigation, Zuoning Han and colleagues from the University of California at San Diego, School of Medicine, show that c-Jun N-terminal kinase plays a critical role in matrix metalloproteinase (MMP) expression and joint destruction in inflammatory (rheumatoid) type arthritis.

Han et al. used a novel selective JNK inhibitor (SP600125 -anthra[1,9-cd]pyrazol-6(2H)-one) and JNK knockout mice to determine the function of JNK in synoviocyte biology and inflammatory arthritis. They found that SP600125 blocked IL-1-stimulated JNK activity in fibroblast-like synoviocytes by directly inhibiting JNK activity. In addition, administration of SP600125 induced near-complete inhibition of radiographic damage that was associated with decreased collagenase ...