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https://doi.org/10.3390/cells9020279
Title: | Synthetic 4-Hydroxy Auxarconjugatin B, a Novel Autophagy Inducer, Attenuates Gouty Inflammation by Inhibiting the NLRP3 Inflammasome | Authors: | Hsieh, CY Li, LH Lam, Y Fang, Z Gan, CH Rao, YK Chiu, HW Wong, WT Ju, TC Chen, FH Chernikov, OV Liu, ML Hsu, CH Hua, KF |
Keywords: | 4-hydroxy auxarconjugatin B NLRP3 inflammasome autophagy gouty inflammation mitochondria Animals Arthritis, Gouty Autophagy CARD Signaling Adaptor Proteins Cell Line Disease Models, Animal Humans Inflammasomes Inflammation Lipopolysaccharides Lysosomes Macrophages Male Mice, Inbred C57BL Mitochondria Models, Biological NLR Family, Pyrin Domain-Containing 3 Protein Organelle Biogenesis Protein Multimerization Pyrroles Sirtuin 1 |
Issue Date: | 23-Jan-2020 | Publisher: | MDPI AG | Citation: | Hsieh, CY, Li, LH, Lam, Y, Fang, Z, Gan, CH, Rao, YK, Chiu, HW, Wong, WT, Ju, TC, Chen, FH, Chernikov, OV, Liu, ML, Hsu, CH, Hua, KF (2020-01-23). Synthetic 4-Hydroxy Auxarconjugatin B, a Novel Autophagy Inducer, Attenuates Gouty Inflammation by Inhibiting the NLRP3 Inflammasome. Cells 9 (2) : E279-. ScholarBank@NUS Repository. https://doi.org/10.3390/cells9020279 | Abstract: | Gouty arthritis results from the generation of uric acid crystals within the joints. These uric acid crystals activate the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome, which is involved in chronic inflammatory diseases, including gouty arthritis. This study identified the polyenylpyrrole derivative 4-hydroxy auxarconjugatin B (4-HAB), a novel autophagy inducer, which attenuated uric acid crystals-mediated activation of the NLRP3 inflammasome in vitro and in vivo. 4-HAB dose-dependently reduced the release of interleukin (IL)-1β, IL-18, active caspase-1 and apoptosis-associated speck-like protein (ASC) in uric acid crystals-activated macrophages. In a mechanistic study, 4-HAB was shown to inhibit uric acid crystals-induced mitochondrial damage, lysosomal rupture and ASC oligomerization. Additionally, 4-HAB inhibited the NLRP3 inflammasome through Sirt1-dependent autophagy induction. Furthermore, the anti-inflammatory properties of 4-HAB were confirmed in a mouse model of uric acid crystals-mediated peritonitis by the reduced levels of neutrophil influx, IL-1β, active caspase-1, IL-6 and MCP-1 in lavage fluids. In conclusion, 4-HAB attenuates gouty inflammation, in part by attenuating activation of the NLRP3 inflammasome through the Sirt1/autophagy induction pathway. | Source Title: | Cells | URI: | https://scholarbank.nus.edu.sg/handle/10635/242991 | ISSN: | 2073-4409 2073-4409 |
DOI: | 10.3390/cells9020279 |
Appears in Collections: | Staff Publications Elements |
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