Synthetic 4-Hydroxy Auxarconjugatin B, a Novel Autophagy Inducer, Attenuates Gouty Inflammation by Inhibiting the NLRP3 Inflammasome
| العنوان: | Synthetic 4-Hydroxy Auxarconjugatin B, a Novel Autophagy Inducer, Attenuates Gouty Inflammation by Inhibiting the NLRP3 Inflammasome |
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| المؤلفون: | Wei Ting Wong, Oleg V. Chernikov, Zhanxiong Fang, Yerra Koteswara Rao, May Lan Liu, Kuo Feng Hua, Tz Chuen Ju, Yulin Lam, Chin Heng Gan, Fang Hsin Chen, Chih Yu Hsieh, Hsiao Wen Chiu, Chung Hua Hsu, Lan Hui Li |
| المصدر: | Cells Cells, Vol 9, Iss 2, p 279 (2020) Volume 9 Issue 2 |
| بيانات النشر: | MDPI, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Lipopolysaccharides, Male, autophagy, Inflammasomes, Inflammation, 4-hydroxy auxarconjugatin B, Pharmacology, Mitochondrion, Models, Biological, Article, Cell Line, chemistry.chemical_compound, Sirtuin 1, In vivo, NLR Family, Pyrin Domain-Containing 3 Protein, medicine, Animals, Humans, Inducer, Pyrroles, lcsh:QH301-705.5, gouty inflammation, Organelle Biogenesis, Arthritis, Gouty, Macrophages, Autophagy, Interleukin, Inflammasome, General Medicine, NLRP3 inflammasome, Mitochondria, CARD Signaling Adaptor Proteins, Mice, Inbred C57BL, Disease Models, Animal, chemistry, lcsh:Biology (General), Uric acid, medicine.symptom, Protein Multimerization, Lysosomes, medicine.drug |
| الوصف: | 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)-1&beta 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-1&beta 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2073-4409 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5612d37fe01e64c091f905ada26d2672Test http://europepmc.org/articles/PMC7072356Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5612d37fe01e64c091f905ada26d2672 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20734409 |
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