Epigallocatechin-3-Gallate Prevents Acute Gout by Suppressing NLRP3 Inflammasome Activation and Mitochondrial DNA Synthesis

Autor:	Joo Young Lee, Yong-Yeon Cho, Hye Suk Lee, Hye-Eun Lee, Youn Bum Park, Han Chang Kang, Gabsik Yang
Rok vydání:	2019
Předmět:	Inflammasomes Interleukin-1beta Pharmaceutical Science Nod Mitochondrion Pharmacology Pyrin domain Catechin Analytical Chemistry Mice 0302 clinical medicine Drug Discovery heterocyclic compounds Receptor innate immunity reactive oxygen species chemistry.chemical_classification 0303 health sciences integumentary system Chemistry Caspase 1 food and beverages Inflammasome macrophages mitochondria Chemistry (miscellaneous) 030220 oncology & carcinogenesis Molecular Medicine medicine.symptom medicine.drug green tea Inflammation DNA Mitochondrial complex mixtures Article lcsh:QD241-441 03 medical and health sciences gout lcsh:Organic chemistry inflammasome NLR Family Pyrin Domain-Containing 3 Protein medicine Animals Humans Physical and Theoretical Chemistry 030304 developmental biology Reactive oxygen species Innate immune system Organic Chemistry Uric Acid Mice Inbred C57BL Disease Models Animal sense organs
Zdroj:	Molecules Volume 24 Issue 11 Molecules, Vol 24, Iss 11, p 2138 (2019)
ISSN:	1420-3049
DOI:	10.3390/molecules24112138
Popis:	Gout is a chronic inflammatory disease evoked by the deposition of monosodium urate (MSU) crystals in joint tissues. The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome is responsible for the gout inflammatory symptoms induced by MSU crystals. We investigated whether epigallocatechin-3-gallate (EGCG) suppresses the activation of the NLRP3 inflammasome, thereby effectively preventing gouty inflammation. EGCG blocked MSU crystal-induced production of caspase-1(p10) and interleukin-1&beta in primary mouse macrophages, indicating its suppressive effect on the NLRP3 inflammasome. In an acute gout mouse model, oral administration of EGCG to mice effectively alleviated gout inflammatory symptoms in mouse foot tissue injected with MSU crystals. The in vivo suppressive effects of EGCG correlated well with the suppression of the NLRP3 inflammasome in mouse foot tissue. EGCG inhibited the de novo synthesis of mitochondrial DNA as well as the production of reactive oxygen species in primary mouse macrophages, contributing to the suppression of the NLRP3 inflammasome. These results show that EGCG suppresses the activation of the NLRP3 inflammasome in macrophages via the blockade of mitochondrial DNA synthesis, contributing to the prevention of gouty inflammation. The inhibitory effects of EGCG on the NLRP3 inflammasome make EGCG a promising therapeutic option for NLRP3-dependent diseases such as gout.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2247660379e1601005b153ad09d0054f https://doi.org/10.3390/molecules24112138 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.