In Vitro Data Supporting a Role for p38a MAPK in RA
Inflammatory cytokine production from many of the cell types present in the rheumatoid joint has been shown to be dependent on the p38a MAPK pathway. The ability of monocytes, synovial fibroblasts, chondrocytes, and osteoblasts to generate IL-6 and IL-8 was shown to be attenuated by p38a MAPK inhibition (Suzuki et al. 2000; Adams et al. 2001a). It is of note that p38a MAPK inhibition does not result in the prevention of proteoglycan loss from IL-1-stimulated articular cartilage (Badger et al. 2000). However, a significant inhibitory effect on iNOS production was demonstrated. Both IL-1 and TNF can stimulate osteoclast-mediated bone resorption through their ability to act directly or indirectly on the osteoclast or their precursors. This indirect activation results from an upregulation of the receptor activator of nuclear factor (NF)-kB ligand (RANK-L), an important osteoclast differentiation, activation, and survival factor present on osteoblasts and stromal cells. Osteoclast-mediated bone resorption stimulated either by IL-1, TNF, or RANK-L have all been shown to be attenuated by p38a MAPK inhibition (Matsumoto et al. 2000; Kumar et al. 2001b). These data offer support to the hypothesis that inhibition of p38a MAPK may not only provide effective anti-inflammatory therapy through their attenuation of cytokine release but may also offer joint protection.
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Everything you wanted to know about. How To Cure Tennis Elbow. Are you an athlete who suffers from tennis elbow? Contrary to popular opinion, most people who suffer from tennis elbow do not even play tennis. They get this condition, which is a torn tendon in the elbow, from the strain of using the same motions with the arm, repeatedly. If you have tennis elbow, you understand how the pain can disrupt your day.