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| 1 | Ticagrelor inhibits the NLRP3 inflammasome to protect against inflammatory disease independent of the P2Y_(12 ) signaling pathway显示文摘Ticagrelor is the first reversibly binding oralP2Y_(12) receptor antagonist to inhibit platelet activation and has been approved by the Food and Drug Administration for the treatment of coronary artery disease. At present, the other pharmacological functions of ticagrelor remain poorly understood. The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome plays a critical role in the innate immune system, but its excessive activation also contributes to the pathogenesis of complex diseases. In this study, we systematically examined the effects of ticagrelor on the NLRP3 inflammasome and found that ticagrelor inhibits NLRP3 inflammasome activation in macrophages independent of its classic inhibitory effect on theP2Y_(12) signaling pathway. Further mechanistic studies demonstrate that ticagrelor attenuates the oligomerization of apoptosis-associated speck-like protein containing a CARD (ASC) by blocking chloride efflux, an effect achieved through the degradation of chloride intracellular channel proteins (CLICs) and blockade of the translocation of CLICs to the plasma membrane. Moreover, experiments on lipopolysaccharide-induced sepsis and alum-induced peritonitis in mice confirmed that ticagrelor mitigates the severity of systemic inflammation independent ofP2Y_(12) receptor antagonism. Importantly, oral administration of ticagrelor rapidly and strongly inhibited NLRP3 inflammasome activation in peripheral blood mononuclear cells from patients with acute coronary syndrome. Overall, our study reveals a novel pharmacological function of ticagrelor in addition to its classic antiplatelet properties, which suggests that ticagrelor may serve as a potential therapeutic agent for use in NLRP3-associated diseases. | Bo Huang Yufeng Qian Shujun Xie Xianhua Ye Hanwen Chen Zhifeng Chen Lihuan Zhang Jinming Xu Hu Hu Shenglin Ma Paul Héroux Di Wang Han-Ming Shen Yihua Wu Dajing Xia | 2021 | Cellular & Molecular Immunology2021，18，5： | 3 |
| 2 | Pregnancy in rheumatology patients exposed to anti-tumour necrosis factor (TNF)-a therapy显示文摘 | Roux C H Brocq O Breuil V C | 2007 | Rheumatology2007，46，4： | 1 |
| 3 | Precise Point Positioning Using IGS Orbit and Clock Products显示文摘 | Jan Kouba Pierre Héroux | 2001 | GPS Solutions2001，，2： | 1 |
| 4 | Nutrition disordersand immunologic parameters:study of the thymus in growing rats显示文摘 | Pallaro A N Roux M E Slobodianik N H | | 0，，： | 1 |
| 5 | Molecular mechanisms underlying Bile acid-stimulated glucagon-like peptide-1 secretion显示文摘 | Parker H E Wallis K Roux C W | 2012 | Br J Pharmacol2012，165，2： | 1 |
| 6 | The gut-brain axis in obesity显示文摘 | Buhmann H Ie Roux CW Bueter M | 2014 | Best Pract Res Clin Gastroenterol2014，28，4： | 1 |
| 7 | Comparison be- tween ultrasound-guided transversus abdominis plane and conventional ilioinguinal/iliohypogastric nerve blocks for day-case open inguinal hernia repair 显示文摘 | Aveline C Le Hetet H Le Roux A | 2011 | Br J Anaesth2011，106，3： | 1 |
| 8 | Ceramic breeder research and development: progress and focus 显示文摘 | Van der Laan J G Kawamura H Roux N | 2000 | Journal of Nuclear Materials2000，，： | 1 |
| 9 | A T-time Petri net extension for real-time task scheduling modeling显示文摘 | Roux O H | 2002 | European Journal of Automation2002，36，7： | 1 |
| 10 | Wavelet Leaders and Bootstrap for Multifraetal Analysis of Images 显示文摘 | WENDT H ROUX S G ABRY P | 2009 | Signal Process2009，89，： | 1 |
| 11 | High and low annealing temperatures increase both specificity and yield in touchdown and stepdown PCR显示文摘 | Hecker K H Roux K H | 1996 | Biotechniques1996，20，3： | 1 |
| 12 | Towards integrated water quality monitoring:Assessment of ecosystem health显示文摘 | ROUX D J VAN VLIET H R VAN VEELEN M | 1993 | Water S A1993，19，4： | 1 |
| 13 | A discussion of fire risk assessment显示文摘 | ROUX H J | 1995 | Fire Risk Assessment1995，19，1： | 1 |
| 14 | Optimization and troubleshooting in PCR显示文摘 | Roux K H | 1995 | PCR Methods Appl1995，4，5： | 1 |
| 15 | Precise Point Positioning Using IGS Orbit and Clock Products显示文摘 | Jan Kouba Pierre Héroux | 2001 | GPS Solutions2001，，2： | 1 |
| 16 | Etanercept com- pared to intraarticular corticosteroid injection in rheuma- toid arthritis : double-blind, randomized pilot study显示文摘 | Roux C H Breuil V Valerio L | 2011 | J Rheumatol2011，38，6： | 1 |
| 17 | Deposition of thin films of Ni-P and Ni-B-P by dynamic chemical plating显示文摘 | Stremsdoerfer G Omidvar H Roux P | 2008 | Journal of Alloys and Compounds2008，466，12： | 1 |
| 18 | High and low annealing temperatures increase both specificity and yield in touchdown and stepdown PCR显示文摘 | HECKER K H ROUX K H | 1996 | Biotechniques1996，20，3： | 1 |
| 19 | Spatial distribution of leaf dry weight per area and leaf nitrogen concentration in relation to local radiation regime within an isolated tree crown显示文摘 | ROUX X SINOQUET H VANDAME M | 1999 | Tree Physiology1999，19，： | 1 |
| 20 | New antibiotics for the treatment of severe staphylococcal infection in the critically ill patient显示文摘 | Schmidt Ioanas M de Roux A Lode H | 2005 | Curr Opin Crit Care2005，11，5： | 1 |
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