{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:59:34Z","timestamp":1789707574020,"version":"4.0.1"},"reference-count":66,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T00:00:00Z","timestamp":1627948800000},"content-version":"vor","delay-in-days":214,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010135","name":"Finska L\u00e4kares\u00e4llskapet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010135","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010133","name":"Aarne Koskelon S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010133","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004337","name":"Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004337","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004212","name":"P\u00e4ivikki ja Sakari Sohlbergin S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004212","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010114","name":"Yrj\u00f6 Jahnssonin S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010114","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004022","name":"Jenny ja Antti Wihurin Rahasto","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004022","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp; Trans Imm"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The NLRP3 inflammasome plays a key role in arterial wall inflammation. In this study, we elucidated the role of serum lipoproteins in the regulation of NLRP3 inflammasome activation by serum amyloid A (SAA) and other inflammasome activators.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The effect of lipoproteins on the NLRP3 inflammasome activation was studied in primary human macrophages and THP\u20101 macrophages. The effect of oxidised low\u2010density lipoprotein (LDL) was examined in an <jats:italic>in\u00a0vivo<\/jats:italic> mouse model of SAA\u2010induced peritoneal inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Native and oxidised high\u2010density lipoproteins (HDL<jats:sub>3<\/jats:sub>) and LDLs inhibited the interaction of SAA with TLR4. HDL<jats:sub>3<\/jats:sub> and LDL inhibited the secretion of interleukin (IL)\u20101\u03b2 and tumor necrosis factor by reducing their transcription. Oxidised forms of these lipoproteins reduced the secretion of mature IL\u20101\u03b2 also by inhibiting the activation of NLRP3 inflammasome induced by SAA, ATP, nigericin and monosodium urate crystals. Specifically, oxidised LDL was found to inhibit the inflammasome complex formation. No cellular uptake of lipoproteins was required, nor intact lipoprotein particles for the inhibitory effect, as the lipid fraction of oxidised LDL was sufficient. The inhibition of NLRP3 inflammasome activation by oxidised LDL was partially dependent on autophagy. Finally, oxidised LDL inhibited the SAA\u2010induced peritoneal inflammation and IL\u20101\u03b2 secretion <jats:italic>in\u00a0vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings reveal that both HDL<jats:sub>3<\/jats:sub> and LDL inhibit the proinflammatory activity of SAA and this inhibition is further enhanced by lipoprotein oxidation. Thus, lipoproteins possess major anti\u2010inflammatory functions that hinder the NLRP3 inflammasome\u2010activating signals, particularly those exerted by SAA, which has important implications in the pathogenesis of cardiovascular diseases.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cti2.1323","type":"journal-article","created":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T10:10:05Z","timestamp":1627985405000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Native and oxidised lipoproteins negatively regulate the serum amyloid A\u2010induced NLRP3 inflammasome activation in human macrophages"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5406-5334","authenticated-orcid":false,"given":"Katariina","family":"Nurmi","sequence":"first","affiliation":[{"name":"Helsinki Rheumatic Diseases and Inflammation Research Group Translational Immunology Research Program University of Helsinki Helsinki University Clinicum Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katri","family":"Niemi","sequence":"additional","affiliation":[{"name":"Wihuri Research Institute Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilona","family":"Kareinen","sequence":"additional","affiliation":[{"name":"Wihuri Research Institute Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristiina","family":"Silventoinen","sequence":"additional","affiliation":[{"name":"Helsinki Rheumatic Diseases and Inflammation Research Group Translational Immunology Research Program University of Helsinki Helsinki University Clinicum Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina B","family":"Lorey","sequence":"additional","affiliation":[{"name":"Helsinki Rheumatic Diseases and Inflammation Research Group Translational Immunology Research Program University of Helsinki Helsinki University Clinicum Helsinki Finland"},{"name":"Wihuri Research Institute Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"Helsinki Rheumatic Diseases and Inflammation Research Group Translational Immunology Research Program University of Helsinki Helsinki University Clinicum Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vesa\u2010Petteri","family":"Kouri","sequence":"additional","affiliation":[{"name":"Helsinki Rheumatic Diseases and Inflammation Research Group Translational Immunology Research Program University of Helsinki Helsinki University Clinicum Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jukka","family":"Parantainen","sequence":"additional","affiliation":[{"name":"Helsinki Rheumatic Diseases and Inflammation Research Group Translational Immunology Research Program University of Helsinki Helsinki University Clinicum Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Juutilainen","sequence":"additional","affiliation":[{"name":"Division of Orthopedics Department of Surgery Helsinki University Central Hospital Vantaa Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katariina","family":"\u00d6\u00f6rni","sequence":"additional","affiliation":[{"name":"Wihuri Research Institute Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petri T","family":"Kovanen","sequence":"additional","affiliation":[{"name":"Wihuri Research Institute Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Nordstr\u00f6m","sequence":"additional","affiliation":[{"name":"Helsinki Rheumatic Diseases and Inflammation Research Group Translational Immunology Research Program University of Helsinki Helsinki University Clinicum Helsinki Finland"},{"name":"Internal Medicine and Rehabilitation University of Helsinki and Helsinki University Hospital Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sampsa","family":"Matikainen","sequence":"additional","affiliation":[{"name":"Helsinki Rheumatic Diseases and Inflammation Research Group Translational Immunology Research Program University of Helsinki Helsinki University Clinicum Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kari K","family":"Eklund","sequence":"additional","affiliation":[{"name":"Helsinki Rheumatic Diseases and Inflammation Research Group Translational Immunology Research Program University of Helsinki Helsinki University Clinicum Helsinki Finland"},{"name":"Division of Rheumatology Department of Medicine Helsinki University Hospital Helsinki Finland"},{"name":"Orton Orthopaedic Hospital Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/002215549804601206"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOL.0000000000000616"},{"key":"e_1_2_9_4_1","first-page":"785","article-title":"Local expression of acute phase serum amyloid A mRNA in rheumatoid arthritis synovial tissue and cells","volume":"26","author":"Kumon Y","year":"1999","journal-title":"J Rheumatol"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar78"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-019-0169-2"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-020-01325-1"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2011.00186"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3083.1998.00394.x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.105.022103"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2009.05.007"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002843"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1100500"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.2143"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-05-1431"},{"key":"e_1_2_9_16_1","first-page":"752","article-title":"Serum amyloid A activates nuclear factor\u2010kappaB in rheumatoid synovial fibroblasts through binding to receptor of advanced glycation end\u2010products","volume":"35","author":"Okamoto H","year":"2008","journal-title":"J Rheumatol"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2006.01.001"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1707914"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0165-0"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a036392"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.01.018"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02188"},{"key":"e_1_2_9_23_1","first-page":"382","article-title":"Characterization of amyloid related protein SAA complexed with serum lipoproteins (apoSAA)","volume":"50","author":"Marhaug G","year":"1982","journal-title":"Clin Exp Immunol"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M300414-JLR200"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.1987.tb02203.x"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.007526"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02762011000800014"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)75675-0"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2004.01.030"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2006.09.005"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOL.0b013e32834adadb"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.140.7.2267"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601363"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.3105cm1"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2014.03.015"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1159\/000448894"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2015.1037061"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.202911"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2215"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.002428"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12638"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1403044"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.3.1852"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-42298-4"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10030625"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.02.011"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-018-0244-y"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1935"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08938"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2012.07.011"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2639"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2017.09.019"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011765"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M037861"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2010.05380.x"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(92)90181-F"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.181743"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20151570"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2930"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI103182"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)52451-6"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehi706"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)64849-5"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)34320-5"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M800196-JLR200"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201600189"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0078537"}],"container-title":["Clinical &amp; Translational Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cti2.1323","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cti2.1323","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cti2.1323","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T15:31:25Z","timestamp":1693323085000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cti2.1323"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":66,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1002\/cti2.1323"],"URL":"https:\/\/doi.org\/10.1002\/cti2.1323","archive":["Portico"],"relation":{},"ISSN":["2050-0068","2050-0068"],"issn-type":[{"value":"2050-0068","type":"print"},{"value":"2050-0068","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"2020-12-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1323"}}