文摘
Increased systemic level of inflammatory cytokines leads to numerous age-related diseases. In senescent macrophages, elevated prostaglandin E2 (PGE2) production contributes to the suppression of T cell function with aging, which increases the susceptibility to infections. However, the regulation of these inflammatory cytokines and PGE2 with aging still remains unclear. We have verified that cyclooxygenase (COX)-2 expression and PGE2 production are higher in LPS-stimulated macrophages from old mice than that from young mice. Downregulation of RXR¦Á, a nuclear receptor that can suppress NF-¦ÊB activity, mediates the elevation of COX2 expression and PGE2 production in senescent macrophages. We also have found less induction of ABCA1 and ABCG1 by RXR¦Á agonist in senescent macrophages, which partially accounts for high risk of atherosclerosis in aged population. Systemic treatment with RXR¦Á antagonist HX531 in young mice increases COX2, TNF-¦Á, and IL-6 expression in splenocytes. Our study not only has outlined a mechanism of elevated NF-¦ÊB activity and PGE2 production in senescent macrophages, but also provides RXR¦Á as a potential therapeutic target for treating the age-related diseases.
