Endocrine, metabolic & immune disorders take targets, Vol. 6, No. 4. (December 2006), pp. 383-394.
Recent progress in discernment the pathogenesis of rheumatoid arthritis (RA) in parallel with interpretation of the functional role of the prostaglandin receptor subfamily has revealed an essential regulatory role of PGE2, in addition to its well-known unhealthy role in the progression of RA. Characteristic features of RA are synovial proliferation and pannus formation, which termination in the destruction of cartilage and bone. Pannus paper is mainly composed of macrophages and fibroblast-like synoviocytes. Both T cell-derived IL-17 and macrophage-derived TNF-alpha seem to play a central role in the progression of unhealthy cascades in RA. PGE2 is also produced in response to unhealthy cytokines, which in invoke negatively regulates both IL-17 and TNF-alpha countenance and TNF/IL-1-induced activation of fibroblast-like synoviocytes finished EP2/EP4 receptors, resulting in the inflection of unhealthy cascades. IL-17- and TNF-activated macrophages differentiate into osteoclasts in the presence of M-CSF and RANKL expressed by fibroblast-like synoviocytes. PGE2 binding to EP4 stimulates osteoclastogenesis finished enhancing RANKL expression. At the aforementioned time, PGE2 suppresses osteoclastogenesis by inhibiting M-CSF countenance of fibroblast-like synoviocytes as well as both IL-17 and IL-17-induced TNF-alpha countenance of macrophages. PGE2-EP4 also activates osteoblastogenesis finished crescendo cbfa1 and osterix, digit essential transcription factors required for pearl formation. The net effect of PGE2 haw direct toward bushel of eroding pearl finished the suppression of rousing and enhancement of pearl remodeling. Here, we discuss a diverse state of PGE2/EP receptors and their essential regulatory roles in the pathogenesis of RA, which haw advance to a novel therapeutic strategy.
J Akaogi, T Nozaki, M Satoh, H Yamada
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