Endocrine, metabolic & immune disorders take targets, Vol. 6, No. 4. (December 2006), pp. 383-394.
Recent advancement in discernment the pathogenesis of rheumatoid arthritis (RA) in parallel with elucidation of the useful persona of the prostaglandin receptor subfamily has revealed an important restrictive persona of PGE2, in constituent to its well-known unhealthy persona in the advancement of RA. Characteristic features of RA are synovial proliferation and pannus formation, which termination in the conclusion of cartilage and bone. Pannus paper is mainly imperturbable of macrophages and fibroblast-like synoviocytes. Both T cell-derived IL-17 and macrophage-derived TNF-alpha seem to play a central persona in the advancement of unhealthy cascades in RA. PGE2 is also produced in salutation to unhealthy cytokines, which in turn negatively regulates both IL-17 and TNF-alpha expression and TNF/IL-1-induced activation of fibroblast-like synoviocytes through EP2/EP4 receptors, resulting in the inflection of unhealthy cascades. IL-17- and TNF-activated macrophages differentiate into osteoclasts in the proximity of M-CSF and RANKL spoken by fibroblast-like synoviocytes. PGE2 binding to EP4 stimulates osteoclastogenesis through enhancing RANKL expression. At the same time, PGE2 suppresses osteoclastogenesis by inhibiting M-CSF expression of fibroblast-like synoviocytes as well as both IL-17 and IL-17-induced TNF-alpha expression of macrophages. PGE2-EP4 also activates osteoblastogenesis through crescendo cbfa1 and osterix, digit primary transcription factors required for pearl formation. The gain effect of PGE2 haw direct toward bushel of wearing pearl through the suppression of inflammation and improvement of pearl remodeling. Here, we discuss a diverse action of PGE2/EP receptors and their important restrictive roles in the pathogenesis of RA, which haw advance to a new therapeutic strategy.
J Akaogi, T Nozaki, M Satoh, H Yamada
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