The stressed synovium

This review focuses on the mechanisms of stress response in the synovial ti ssue of rheumatoid arthritis. The major stress factors, such as heat stress , shear stress, proinflammatory cytokines and oxidative stress, are discuss ed and reviewed, focusing on their potential to induce a stress response in the synovial tissue. Several pathways of stress signalling molecules are f ound to be activated in the synovial membrane of rheumatoid arthritis; of t hese the most important examples are heat shock proteins, mitogen-activated protein kinases, stress-activated protein kinases and molecules involved i n the oxidative stress pathways. The expression of these pathways in vitro and in vivo as well as the consequences of stress signalling in the rheumat oid synovium are discussed. Stress signalling is part of a cellular respons e to potentially harmful stimuli and thus is essentially involved in the pr ocess of synovitis. Stress signalling pathways are therefore new and promis ing targets of future anti-rheumatic therapies.