Resveratrol inhibits the acetylated α-tubulin-mediated assembly of the NLRP3-inflammasome
| العنوان: | Resveratrol inhibits the acetylated α-tubulin-mediated assembly of the NLRP3-inflammasome |
|---|---|
| المؤلفون: | Michihiro Takahama, Tatsuya Saitoh, Shizuo Akira, Takuma Misawa, Tatsuya Kozaki, Sehoon Park |
| المصدر: | International Immunology. 27:425-434 |
| بيانات النشر: | Oxford University Press (OUP), 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Inflammasomes, Phytochemicals, Immunology, Apoptosis, Wine, Resveratrol, Mitochondrion, Endoplasmic Reticulum, Pyrin domain, Mice, chemistry.chemical_compound, Tubulin, NLR Family, Pyrin Domain-Containing 3 Protein, Stilbenes, medicine, Animals, Immunology and Allergy, Vitis, Caspase, Inflammation, integumentary system, biology, Macrophages, Endoplasmic reticulum, food and beverages, Signal transducing adaptor protein, Inflammasome, General Medicine, Immunity, Innate, Mitochondria, Cell biology, Mice, Inbred C57BL, chemistry, Biochemistry, Acetylation, Caspases, biology.protein, Female, Apoptosis Regulatory Proteins, Carrier Proteins, Signal Transduction, medicine.drug |
| الوصف: | With its adaptor protein apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), Nod-like receptor family, pyrin domain containing 3 (NLRP3) forms the inflammasome and mediates inflammatory innate immune responses. Development of an anti-inflammatory drug targeting the NLRP3-inflammasome is urgently required because its aberrant activation often causes inflammatory diseases, including gout. We show that resveratrol, a natural polyphenol in grapes and wine, is a safe and effective phytochemical that inhibits NLRP3-inflammasome activation. Resveratrol inhibits the accumulation of acetylated α-tubulin caused by mitochondrial damage in macrophages stimulated with inducers of the NLRP3-inflammasome. Consequently, resveratrol inhibits the acetylated-α-tubulin-mediated spatial arrangement of mitochondria and their subsequent contact with the endoplasmic reticulum (ER), causing insufficient assembly of ASC on the mitochondria and NLRP3 on the ER. These findings indicate that resveratrol targets the generation of an optimal site for the assembly of NLRP3 and ASC, thus inhibiting NLRP3-inflammasome activation. Therefore, resveratrol could be an effective medication for the treatment of NLRP3-related inflammatory diseases. |
| تدمد: | 1460-2377 0953-8178 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e7573e3fc53fed655fb9ceea632d421cTest https://doi.org/10.1093/intimm/dxv018Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e7573e3fc53fed655fb9ceea632d421c |
| قاعدة البيانات: | OpenAIRE |
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Development of an anti-inflammatory drug targeting the NLRP3-inflammasome is urgently required because its aberrant activation often causes inflammatory diseases, including gout. We show that resveratrol, a natural polyphenol in grapes and wine, is a safe and effective phytochemical that inhibits NLRP3-inflammasome activation. Resveratrol inhibits the accumulation of acetylated α-tubulin caused by mitochondrial damage in macrophages stimulated with inducers of the NLRP3-inflammasome. Consequently, resveratrol inhibits the acetylated-α-tubulin-mediated spatial arrangement of mitochondria and their subsequent contact with the endoplasmic reticulum (ER), causing insufficient assembly of ASC on the mitochondria and NLRP3 on the ER. These findings indicate that resveratrol targets the generation of an optimal site for the assembly of NLRP3 and ASC, thus inhibiting NLRP3-inflammasome activation. 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