【摘 要】
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OBJECTIVE Interleukin (IL)-1β, one of the principal inflammatory cytokines mainly secreted by mono?cytes and macrophages, is produced by cleavage of the inactive pro-IL-1βprecursor by caspase-1 via the NLRP3 inflam?masome complex. The fruits of Garcinia c
【机 构】
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State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,U
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OBJECTIVE Interleukin (IL)-1β, one of the principal inflammatory cytokines mainly secreted by mono?cytes and macrophages, is produced by cleavage of the inactive pro-IL-1βprecursor by caspase-1 via the NLRP3 inflam?masome complex. The fruits of Garcinia cambogia (Clusiaceae) are widely developed as health products for anti-obese purpose. 14-deoxygarcinol (DOG) is a polyisoprenylated benzophenone from the fruits of G. cambogia, which showed potent anti-inflammatory effect in our previous study. The objective of this study was to explore the anti-inflammatory mechanism of DOG and its roles in alleviating adipose tissue inflammation and insulin resistance. METHODS The anti-inflammatory effect of DOG was evaluated on LPS plus nigericin-induced THP-1 macrophages. The expression of NLRP3 inflammasome complex proteins was analyzed by Western blotting, immunofluorescence staining and co-immu?noprecipitation. The pro-inflammatory cytokines levels were determined by ELISA kits. RESULTS DOG increased the expression of Sirtuin 2 (SIRT2) deacetylase and enhanced its deacetylating activity to suppress the NLRP3 inflamma?some activation and IL-1βsecretion in THP-1 macrophages. Moreover, DOG attenuated macrophage conditioned medium-induced inflammatory responses in adipocytes and blocked THP-1 macrophages migration towards 3T3-L1 adipocytes. CONCLUSION DOG attenuated the inflammatory crosstalk between macrophages and adipocytes through SIRT2-mediated NLRP3 inflammasome inhibition, which might be used for the treatment of adipose tissue inflammation-related metabolic disorders.
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