{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:26:08Z","timestamp":1790630768267,"version":"4.1.0"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T00:00:00Z","timestamp":1564531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T00:00:00Z","timestamp":1564531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000050","name":"U.S. Department of Health &amp; Human Services | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL128268"],"award-info":[{"award-number":["R01 HL128268"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"U.S. Department of Health &amp; Human Services | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL130085"],"award-info":[{"award-number":["R01 HL130085"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["SDG25710128"],"award-info":[{"award-number":["SDG25710128"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Miltefosine is an FDA approved oral drug for treating cutaneous and visceral leishmaniasis. Leishmania is a flagellated protozoa, which infects and differentiates in macrophages. Here, we studied the effects of Miltefosine on macrophage\u2019s lipid homeostasis, autophagy, and NLRP3 inflammasome assembly\/activity. Miltefosine treatment conferred multiple effects on macrophage lipid homeostasis leading to increased cholesterol release from cells, increased lipid-raft disruption, decreased phosphatidylserine (PS) flip from the cell-surface, and redistribution of phosphatidylinositol 4,5-bisphosphate (PIP2) from the plasma membrane to actin rich regions in the cells. Enhanced basal autophagy, lipophagy and mitophagy was observed in cells treated with Miltefosine vs. control. Miltefosine treated cells showed marked increased in phosphorylation of kinases involved in autophagy induction such as; Adenosine monophosphate-activated protein kinase (AMPK) and Unc-51 like autophagy activating kinase (ULK1). The Toll like receptor (TLR) signaling pathway was blunted by Miltefosine treatment, resulting in decreased TLR4 recruitment to cell-surface and ~75% reduction in LPS induced pro-IL-1\u03b2 mRNA levels. Miltefosine reduced endotoxin-mediated mitochondrial reactive oxygen species and protected the mitochondrial membrane potential. Miltefosine treatment induced mitophagy and dampened NLRP3 inflammasome assembly. Collectively, our data shows that Miltefosine induced ABCA1 mediated cholesterol release, induced AMPK phosphorylation and mitophagy, while dampening NLRP3 inflammasome assembly and IL-1\u03b2 release.<\/jats:p>","DOI":"10.1038\/s41598-019-47610-w","type":"journal-article","created":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T06:02:57Z","timestamp":1564552977000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Miltefosine increases macrophage cholesterol release and inhibits NLRP3-inflammasome assembly and IL-1\u03b2 release"],"prefix":"10.1038","volume":"9","author":[{"given":"Amanda J.","family":"Iacano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harvey","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennie E.","family":"Hazen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Andro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kailash","family":"Gulshan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,7,31]]},"reference":[{"key":"47610_CR1","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/j.cell.2011.04.005","volume":"145","author":"KJ Moore","year":"2011","unstructured":"Moore, K. J. & Tabas, I. Macrophages in the pathogenesis of atherosclerosis. Cell 145, 341\u2013355 (2011).","journal-title":"Cell"},{"key":"47610_CR2","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1038\/nature08938","volume":"464","author":"P Duewell","year":"2010","unstructured":"Duewell, P. et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464, 1357\u20131361 (2010).","journal-title":"Nature"},{"key":"47610_CR3","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1161\/hc0902.104353","volume":"105","author":"P Libby","year":"2002","unstructured":"Libby, P., Ridker, P. M. & Maseri, A. Inflammation and atherosclerosis. Circulation 105, 1135\u20131143 (2002).","journal-title":"Circulation"},{"key":"47610_CR4","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1038\/nri3793","volume":"15","author":"AR Tall","year":"2015","unstructured":"Tall, A. R. & Yvan-Charvet, L. Cholesterol, inflammation and innate immunity. Nat Rev Immunol 15, 104\u2013116 (2015).","journal-title":"Nat Rev Immunol"},{"key":"47610_CR5","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1016\/j.cmet.2012.02.011","volume":"15","author":"B Razani","year":"2012","unstructured":"Razani, B. et al. Autophagy links inflammasomes to atherosclerotic progression. Cell metabolism 15, 534\u2013544 (2012).","journal-title":"Cell metabolism"},{"key":"47610_CR6","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1056\/NEJMoa1707914","volume":"377","author":"PM Ridker","year":"2017","unstructured":"Ridker, P. M. et al. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. The New England journal of medicine 377, 1119\u20131131 (2017).","journal-title":"The New England journal of medicine"},{"key":"47610_CR7","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/j.cmet.2012.01.022","volume":"15","author":"X Liao","year":"2012","unstructured":"Liao, X. et al. Macrophage autophagy plays a protective role in advanced atherosclerosis. Cell metabolism 15, 545\u2013553 (2012).","journal-title":"Cell metabolism"},{"key":"47610_CR8","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1016\/j.cmet.2011.03.023","volume":"13","author":"M Ouimet","year":"2011","unstructured":"Ouimet, M. et al. Autophagy regulates cholesterol efflux from macrophage foam cells via lysosomal acid lipase. Cell metabolism 13, 655\u2013667 (2011).","journal-title":"Cell metabolism"},{"key":"47610_CR9","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1194\/jlr.M600167-JLR200","volume":"48","author":"H Berrougui","year":"2007","unstructured":"Berrougui, H., Isabelle, M., Cloutier, M., Grenier, G. & Khalil, A. Age-related impairment of HDL-mediated cholesterol efflux. Journal of lipid research 48, 328\u2013336 (2007).","journal-title":"Journal of lipid research"},{"key":"47610_CR10","doi-asserted-by":"publisher","first-page":"2576","DOI":"10.1093\/jac\/dks275","volume":"67","author":"TP Dorlo","year":"2012","unstructured":"Dorlo, T. P., Balasegaram, M., Beijnen, J. H. & de Vries, P. J. Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis. J Antimicrob Chemother 67, 2576\u20132597 (2012).","journal-title":"J Antimicrob Chemother"},{"key":"47610_CR11","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.yexcr.2015.12.012","volume":"340","author":"P Rios-Marco","year":"2016","unstructured":"Rios-Marco, P., Marco, C., Cueto, F. J., Carrasco, M. P. & Jimenez-Lopez, J. M. Pleiotropic effects of antitumour alkylphospholipids on cholesterol transport and metabolism. Exp Cell Res 340, 81\u201390 (2016).","journal-title":"Exp Cell Res"},{"key":"47610_CR12","doi-asserted-by":"publisher","DOI":"10.1186\/1476-511X-9-33","volume":"9","author":"JM Jimenez-Lopez","year":"2010","unstructured":"Jimenez-Lopez, J. M., Rios-Marco, P., Marco, C., Segovia, J. L. & Carrasco, M. P. Alterations in the homeostasis of phospholipids and cholesterol by antitumor alkylphospholipids. Lipids in health and disease 9, 33 (2010).","journal-title":"Lipids in health and disease"},{"key":"47610_CR13","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1038\/jid.2008.248","volume":"129","author":"K Weller","year":"2009","unstructured":"Weller, K. et al. Miltefosine inhibits human mast cell activation and mediator release both in vitro and in vivo. J Invest Dermatol 129, 496\u2013498 (2009).","journal-title":"J Invest Dermatol"},{"key":"47610_CR14","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1124\/jpet.110.172890","volume":"336","author":"P Rios-Marco","year":"2011","unstructured":"Rios-Marco, P., Jimenez-Lopez, J. M., Marco, C., Segovia, J. L. & Carrasco, M. P. Antitumoral alkylphospholipids induce cholesterol efflux from the plasma membrane in HepG2 cells. J Pharmacol Exp Ther 336, 866\u2013873 (2011).","journal-title":"J Pharmacol Exp Ther"},{"key":"47610_CR15","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1161\/CIRCRESAHA.116.308856","volume":"119","author":"K Gulshan","year":"2016","unstructured":"Gulshan, K. et al. PI(4,5)P2 Is Translocated by ABCA1 to the Cell Surface Where It Mediates Apolipoprotein A1 Binding and Nascent HDL Assembly. Circulation research 119, 827\u2013838 (2016).","journal-title":"Circulation research"},{"key":"47610_CR16","doi-asserted-by":"publisher","first-page":"26321","DOI":"10.1074\/jbc.M413993200","volume":"280","author":"N Alder-Baerens","year":"2005","unstructured":"Alder-Baerens, N. et al. Headgroup-specific exposure of phospholipids in ABCA1-expressing cells. The Journal of biological chemistry 280, 26321\u201326329 (2005).","journal-title":"The Journal of biological chemistry"},{"key":"47610_CR17","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1194\/jlr.M800345-JLR200","volume":"50","author":"S Nandi","year":"2009","unstructured":"Nandi, S. et al. ABCA1-mediated cholesterol efflux generates microparticles in addition to HDL through processes governed by membrane rigidity. Journal of lipid research 50, 456\u2013466 (2009).","journal-title":"Journal of lipid research"},{"key":"47610_CR18","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1194\/jlr.M300336-JLR200","volume":"45","author":"JD Smith","year":"2004","unstructured":"Smith, J. D. et al. ABCA1 mediates concurrent cholesterol and phospholipid efflux to apolipoprotein A-I. Journal of lipid research 45, 635\u2013644 (2004).","journal-title":"Journal of lipid research"},{"key":"47610_CR19","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1194\/jlr.M500531-JLR200","volume":"47","author":"PT Duong","year":"2006","unstructured":"Duong, P. T. et al. Characterization of nascent HDL particles and microparticles formed by ABCA1-mediated efflux of cellular lipids to apoA-I. Journal of lipid research 47, 832\u2013843 (2006).","journal-title":"Journal of lipid research"},{"key":"47610_CR20","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/35036052","volume":"1","author":"K Simons","year":"2000","unstructured":"Simons, K. & Toomre, D. Lipid rafts and signal transduction. Nature reviews. Molecular cell biology 1, 31\u201339 (2000).","journal-title":"Nature reviews. Molecular cell biology"},{"key":"47610_CR21","doi-asserted-by":"publisher","first-page":"3196","DOI":"10.1194\/jlr.M006486","volume":"51","author":"X Zhu","year":"2010","unstructured":"Zhu, X. et al. Macrophage ABCA1 reduces MyD88-dependent Toll-like receptor trafficking to lipid rafts by reduction of lipid raft cholesterol. Journal of lipid research 51, 3196\u20133206 (2010).","journal-title":"Journal of lipid research"},{"key":"47610_CR22","doi-asserted-by":"publisher","first-page":"1837","DOI":"10.1161\/CIRCULATIONAHA.108.793869","volume":"118","author":"L Yvan-Charvet","year":"2008","unstructured":"Yvan-Charvet, L. et al. Increased inflammatory gene expression in ABC transporter-deficient macrophages: free cholesterol accumulation, increased signaling via toll-like receptors, and neutrophil infiltration of atherosclerotic lesions. Circulation 118, 1837\u20131847 (2008).","journal-title":"Circulation"},{"key":"47610_CR23","doi-asserted-by":"publisher","first-page":"36091","DOI":"10.1074\/jbc.M602247200","volume":"281","author":"YD Landry","year":"2006","unstructured":"Landry, Y. D. et al. ATP-binding cassette transporter A1 expression disrupts raft membrane microdomains through its ATPase-related functions. The Journal of biological chemistry 281, 36091\u201336101 (2006).","journal-title":"The Journal of biological chemistry"},{"key":"47610_CR24","doi-asserted-by":"publisher","first-page":"2337","DOI":"10.1158\/1535-7163.MCT-07-0202","volume":"6","author":"AH van der Luit","year":"2007","unstructured":"van der Luit, A. H. et al. A new class of anticancer alkylphospholipids uses lipid rafts as membrane gateways to induce apoptosis in lymphoma cells. Mol Cancer Ther 6, 2337\u20132345 (2007).","journal-title":"Mol Cancer Ther"},{"key":"47610_CR25","doi-asserted-by":"crossref","unstructured":"Gulshan, K., Brubaker, G., Wang, S., Hazen, S. L. & Smith, J. D. Sphingomyelin Depletion Impairs Anionic Phospholipid Inward Translocation and Induces Cholesterol Efflux. The Journal of biological chemistry (2013).","DOI":"10.1074\/jbc.M113.512244"},{"key":"47610_CR26","doi-asserted-by":"publisher","first-page":"3364","DOI":"10.1194\/jlr.D007336","volume":"51","author":"P Robinet","year":"2010","unstructured":"Robinet, P., Wang, Z., Hazen, S. L. & Smith, J. D. A simple and sensitive enzymatic method for cholesterol quantification in macrophages and foam cells. Journal of lipid research 51, 3364\u20133369 (2010).","journal-title":"Journal of lipid research"},{"key":"47610_CR27","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1126\/science.1196371","volume":"331","author":"DF Egan","year":"2011","unstructured":"Egan, D. F. et al. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science 331, 456\u2013461 (2011).","journal-title":"Science"},{"key":"47610_CR28","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1161\/01.RES.0000261924.76669.36","volume":"100","author":"Y Matsui","year":"2007","unstructured":"Matsui, Y. et al. Distinct roles of autophagy in the heart during ischemia and reperfusion: roles of AMP-activated protein kinase and Beclin 1 in mediating autophagy. Circulation research 100, 914\u2013922 (2007).","journal-title":"Circulation research"},{"key":"47610_CR29","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1038\/ncb2152","volume":"13","author":"J Kim","year":"2011","unstructured":"Kim, J., Kundu, M., Viollet, B. & Guan, K. L. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nature cell biology 13, 132\u2013141 (2011).","journal-title":"Nature cell biology"},{"key":"47610_CR30","doi-asserted-by":"publisher","first-page":"10679","DOI":"10.1073\/pnas.0403249101","volume":"101","author":"KS Michelsen","year":"2004","unstructured":"Michelsen, K. S. et al. Lack of Toll-like receptor 4 or myeloid differentiation factor 88 reduces atherosclerosis and alters plaque phenotype in mice deficient in apolipoprotein E. Proceedings of the National Academy of Sciences of the United States of America 101, 10679\u201310684 (2004).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"47610_CR31","doi-asserted-by":"publisher","first-page":"e08009","DOI":"10.7554\/eLife.08009","volume":"4","author":"A Ito","year":"2015","unstructured":"Ito, A. et al. LXRs link metabolism to inflammation through Abca1-dependent regulation of membrane composition and TLR signaling. eLife 4, e08009 (2015).","journal-title":"eLife"},{"key":"47610_CR32","doi-asserted-by":"publisher","first-page":"e113789","DOI":"10.1371\/journal.pone.0113789","volume":"9","author":"F Dong","year":"2014","unstructured":"Dong, F., Mo, Z., Eid, W., Courtney, K. C. & Zha, X. Akt inhibition promotes ABCA1-mediated cholesterol efflux to ApoA-I through suppressing mTORC1. PloS one 9, e113789 (2014).","journal-title":"PloS one"},{"key":"47610_CR33","doi-asserted-by":"publisher","first-page":"1959","DOI":"10.1093\/eurheartj\/ehv653","volume":"37","author":"A Janoudi","year":"2016","unstructured":"Janoudi, A., Shamoun, F. E., Kalavakunta, J. K. & Abela, G. S. Cholesterol crystal induced arterial inflammation and destabilization of atherosclerotic plaque. European heart journal 37, 1959\u20131967 (2016).","journal-title":"European heart journal"},{"key":"47610_CR34","doi-asserted-by":"publisher","first-page":"36617","DOI":"10.1074\/jbc.M112.407130","volume":"287","author":"C Juliana","year":"2012","unstructured":"Juliana, C. et al. Non-transcriptional priming and deubiquitination regulate NLRP3 inflammasome activation. The Journal of biological chemistry 287, 36617\u201336622 (2012).","journal-title":"The Journal of biological chemistry"},{"key":"47610_CR35","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1038\/nature18590","volume":"535","author":"J Ding","year":"2016","unstructured":"Ding, J. et al. Pore-forming activity and structural autoinhibition of the gasdermin family. Nature 535, 111\u2013116 (2016).","journal-title":"Nature"},{"key":"47610_CR36","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1038\/nature15541","volume":"526","author":"N Kayagaki","year":"2015","unstructured":"Kayagaki, N. et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature 526, 666\u2013671 (2015).","journal-title":"Nature"},{"key":"47610_CR37","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.1161\/CIRCRESAHA.113.301086","volume":"112","author":"M Westerterp","year":"2013","unstructured":"Westerterp, M. et al. Deficiency of ATP-Binding Cassette Transporters A1 and G1 in Macrophages Increases Inflammation and Accelerates Atherosclerosis in Mice. Circulation research 112, 1456\u20131465 (2013).","journal-title":"Circulation research"},{"key":"47610_CR38","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1016\/j.cmet.2017.04.005","volume":"25","author":"M Westerterp","year":"2017","unstructured":"Westerterp, M. et al. Cholesterol Accumulation in Dendritic Cells Links the Inflammasome to Acquired Immunity. Cell metabolism 25, 1294\u20131304 e1296 (2017).","journal-title":"Cell metabolism"},{"key":"47610_CR39","doi-asserted-by":"publisher","first-page":"5230","DOI":"10.4049\/jimmunol.1301490","volume":"191","author":"ME Heid","year":"2013","unstructured":"Heid, M. E. et al. Mitochondrial reactive oxygen species induces NLRP3-dependent lysosomal damage and inflammasome activation. Journal of immunology 191, 5230\u20135238 (2013).","journal-title":"Journal of immunology"},{"key":"47610_CR40","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.immuni.2013.08.001","volume":"39","author":"SS Iyer","year":"2013","unstructured":"Iyer, S. S. et al. Mitochondrial cardiolipin is required for Nlrp3 inflammasome activation. Immunity 39, 311\u2013323 (2013).","journal-title":"Immunity"},{"key":"47610_CR41","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1016\/S0092-8674(00)80696-0","volume":"100","author":"MP Czech","year":"2000","unstructured":"Czech, M. P. PIP2 and PIP3: complex roles at the cell surface. Cell 100, 603\u2013606 (2000).","journal-title":"Cell"},{"key":"47610_CR42","doi-asserted-by":"publisher","first-page":"869","DOI":"10.3892\/ijo.2015.3306","volume":"48","author":"GM Nitulescu","year":"2016","unstructured":"Nitulescu, G. M. et al. Akt inhibitors in cancer treatment: The long journey from drug discovery to clinical use (Review). Int J Oncol 48, 869\u2013885 (2016).","journal-title":"Int J Oncol"},{"key":"47610_CR43","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.tem.2014.03.010","volume":"25","author":"I Sergin","year":"2014","unstructured":"Sergin, I. & Razani, B. Self-eating in the plaque: what macrophage autophagy reveals about atherosclerosis. Trends in endocrinology and metabolism: TEM 25, 225\u2013234 (2014).","journal-title":"Trends in endocrinology and metabolism: TEM"},{"key":"47610_CR44","doi-asserted-by":"publisher","first-page":"a000257","DOI":"10.1101\/cshperspect.a000257","volume":"2","author":"R Sen","year":"2010","unstructured":"Sen, R. & Smale, S. T. Selectivity of the NF-{kappa}B response. Cold Spring Harbor perspectives in biology 2, a000257 (2010).","journal-title":"Cold Spring Harbor perspectives in biology"},{"key":"47610_CR45","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1038\/ni.2070","volume":"12","author":"ST Smale","year":"2011","unstructured":"Smale, S. T. Hierarchies of NF-kappaB target-gene regulation. Nature immunology 12, 689\u2013694 (2011).","journal-title":"Nature immunology"},{"key":"47610_CR46","doi-asserted-by":"publisher","first-page":"43019","DOI":"10.1074\/jbc.M112.388694","volume":"287","author":"EM Wier","year":"2012","unstructured":"Wier, E. M., Neighoff, J., Sun, X., Fu, K. & Wan, F. Identification of an N-terminal truncation of the NF-kappaB p65 subunit that specifically modulates ribosomal protein S3-dependent NF-kappaB gene expression. The Journal of biological chemistry 287, 43019\u201343029 (2012).","journal-title":"The Journal of biological chemistry"},{"key":"47610_CR47","doi-asserted-by":"crossref","unstructured":"Chen, J. & Chen, Z. J. PtdIns4P on dispersed trans-Golgi network mediates NLRP3 inflammasome activation. Nature (2018).","DOI":"10.1038\/s41586-018-0761-3"},{"key":"47610_CR48","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10555","volume":"7","author":"M Karmakar","year":"2016","unstructured":"Karmakar, M., Katsnelson, M. A., Dubyak, G. R. & Pearlman, E. Neutrophil P2X7 receptors mediate NLRP3 inflammasome-dependent IL-1beta secretion in response to ATP. Nature communications 7, 10555 (2016).","journal-title":"Nature communications"},{"key":"47610_CR49","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1038\/nature16959","volume":"530","author":"Y He","year":"2016","unstructured":"He, Y., Zeng, M. Y., Yang, D., Motro, B. & Nunez, G. NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux. Nature 530, 354\u2013357 (2016).","journal-title":"Nature"},{"key":"47610_CR50","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/nature09663","volume":"469","author":"R Zhou","year":"2011","unstructured":"Zhou, R., Yazdi, A. S., Menu, P. & Tschopp, J. A role for mitochondria in NLRP3 inflammasome activation. Nature 469, 221\u2013225 (2011).","journal-title":"Nature"},{"key":"47610_CR51","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1038\/s41586-018-0372-z","volume":"560","author":"Z Zhong","year":"2018","unstructured":"Zhong, Z. et al. New mitochondrial DNA synthesis enables NLRP3 inflammasome activation. Nature 560, 198\u2013203 (2018).","journal-title":"Nature"},{"key":"47610_CR52","doi-asserted-by":"crossref","unstructured":"Sanchez-Lopez, E. et al. Choline Uptake and Metabolism Modulate Macrophage IL-1beta and IL-18 Production. Cell metabolism (2019).","DOI":"10.1016\/j.cmet.2019.03.011"},{"key":"47610_CR53","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/0014-5793(91)81018-4","volume":"288","author":"R Haase","year":"1991","unstructured":"Haase, R., Wieder, T., Geilen, C. C. & Reutter, W. The phospholipid analogue hexadecylphosphocholine inhibits phosphatidylcholine biosynthesis in Madin-Darby canine kidney cells. FEBS letters 288, 129\u2013132 (1991).","journal-title":"FEBS letters"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-47610-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-47610-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-47610-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T07:10:06Z","timestamp":1671261006000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-47610-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,31]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["47610"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-47610-w","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/430769","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,31]]},"assertion":[{"value":"6 February 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 June 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 July 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A patent application related to this work has been filed by the Cleveland Clinic that lists K.G. and J.D.S. as inventors. Authors declare no non-financial competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"11128"}}