{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T07:09:11Z","timestamp":1790233751705,"version":"4.1.0"},"reference-count":65,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,7,31]],"date-time":"2015-07-31T00:00:00Z","timestamp":1438300800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Health and Medical Research Council of Australia (NHMRC)","award":["APP1062721"],"award-info":[{"award-number":["APP1062721"]}]},{"name":"National Health and Medical Research Council of Australia (NHMRC)","award":["APP1006017"],"award-info":[{"award-number":["APP1006017"]}]},{"name":"National Health and Medical Research Council of Australia (NHMRC)","award":["350327"],"award-info":[{"award-number":["350327"]}]},{"name":"National Health and Medical Research Council of Australia (NHMRC)","award":["APP1041766"],"award-info":[{"award-number":["APP1041766"]}]},{"name":"Group-of-Eight Australia (Go8)\/German Academic Exchange Service (DAAD) Joint Research-Cooperation Scheme"},{"name":"Monash Graduate Scholarship","award":["5129593"],"award-info":[{"award-number":["5129593"]}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2016,2]]},"abstract":"Background and Purpose<\/jats:title>Inflammasomes are multimeric complexes that facilitate caspase\u20101\u2010mediated processing of the pro\u2010inflammatory cytokines IL<\/jats:styled-content>\u20101\u03b2 and IL<\/jats:styled-content>\u201018. Clinical hypertension is associated with renal inflammation and elevated circulating levels of IL<\/jats:styled-content>\u20101\u03b2 and IL<\/jats:styled-content>\u201018. Therefore, we investigated whether hypertension in mice is associated with increased expression and\/or activation of the inflammasome in the kidney, and if inhibition of inflammasome activity reduces BP<\/jats:styled-content>, markers of renal inflammation and fibrosis.<\/jats:p><\/jats:sec>Experimental Approach<\/jats:title>Wild\u2010type and inflammasome\u2010deficient ASC<\/jats:styled-content>\u2212\/\u2212<\/jats:sup> mice were uninephrectomized and received deoxycorticosterone acetate and saline to drink (1K<\/jats:styled-content>\/DOCA<\/jats:styled-content>\/salt). Control mice were uninephrectomized but received a placebo pellet and water. BP<\/jats:styled-content> was measured by tail cuff; renal expression of inflammasome subunits and inflammatory markers was measured by real\u2010time PCR<\/jats:styled-content> and immunoblotting; macrophage and collagen accumulation was assessed by immunohistochemistry.<\/jats:p><\/jats:sec>Key Results<\/jats:title>1K<\/jats:styled-content>\/DOCA<\/jats:styled-content>\/salt\u2010induced hypertension in mice was associated with increased renal mRNA<\/jats:styled-content> expression of inflammasome subunits NLRP<\/jats:styled-content>3, ASC<\/jats:styled-content> and pro\u2010caspase\u20101, and the cytokine, pro\u2010IL<\/jats:styled-content>\u20101\u03b2, as well as protein levels of active caspase\u20101 and mature IL<\/jats:styled-content>\u20101\u03b2. Following treatment with 1K<\/jats:styled-content>\/DOCA<\/jats:styled-content>\/salt, ASC<\/jats:styled-content>\u2212\/\u2212<\/jats:sup> mice displayed blunted pressor responses and were also protected from increases in renal expression of IL<\/jats:styled-content>\u20106, IL<\/jats:styled-content>\u201017A, CCL<\/jats:styled-content>2, ICAM<\/jats:styled-content>\u20101 and VCAM<\/jats:styled-content>\u20101, and accumulation of macrophages and collagen. Finally, treatment with a novel inflammasome inhibitor, MCC<\/jats:styled-content>950, reversed hypertension in 1K<\/jats:styled-content>\/DOCA<\/jats:styled-content>\/salt\u2010treated mice.<\/jats:p><\/jats:sec>Conclusions and Implications<\/jats:title>Renal inflammation, fibrosis and elevated BP<\/jats:styled-content> induced by 1K<\/jats:styled-content>\/DOCA<\/jats:styled-content>\/salt treatment are dependent on inflammasome activity, highlighting the inflammasome\/IL<\/jats:styled-content>\u20101\u03b2 pathway as a potential therapeutic target in hypertension.<\/jats:p><\/jats:sec>Linked Articles<\/jats:title>This article is part of a themed section on Inflammation: maladies, models, mechanisms and molecules. To view the other articles in this section visit http:\/\/dx.doi.org\/10.1111\/bph.2016.173.issue-4<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13230","type":"journal-article","created":{"date-parts":[[2015,6,23]],"date-time":"2015-06-23T11:21:43Z","timestamp":1435058503000},"page":"752-765","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":175,"title":["Inflammasome activity is essential for one kidney\/deoxycorticosterone acetate\/salt\u2010induced hypertension in mice"],"prefix":"10.1111","volume":"173","author":[{"given":"S M","family":"Krishnan","sequence":"first","affiliation":[{"name":"Department of Pharmacology Monash University Clayton Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J K","family":"Dowling","sequence":"additional","affiliation":[{"name":"Centre for Innate Immunity and Infectious Diseases MIMR\u2010PHI Institute of Medical Research Clayton Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y H","family":"Ling","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Monash University Clayton Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Diep","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Monash University Clayton Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C T","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Monash University Clayton Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Ferens","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Monash University Clayton Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M M","family":"Kett","sequence":"additional","affiliation":[{"name":"Department of Physiology Monash University Clayton Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Pinar","sequence":"additional","affiliation":[{"name":"Centre for Innate Immunity and Infectious Diseases MIMR\u2010PHI Institute of Medical Research Clayton Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C S","family":"Samuel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Monash University Clayton Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Vinh","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Monash University Clayton Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T V","family":"Arumugam","sequence":"additional","affiliation":[{"name":"Department of Physiology Yong Loo Lin School of Medicine National University of Singapore Singapore"},{"name":"School of Pharmacy Sungkyunkwan University Suwon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T D","family":"Hewitson","sequence":"additional","affiliation":[{"name":"Department of Nephrology Royal Melbourne Hospital Parkville Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B K","family":"Kemp\u2010Harper","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Monash University Clayton Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A A B","family":"Robertson","sequence":"additional","affiliation":[{"name":"Division of Chemistry and Structural Biology Institute for Molecular Bioscience The University of Queensland Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M A","family":"Cooper","sequence":"additional","affiliation":[{"name":"Division of Chemistry and Structural Biology Institute for Molecular Bioscience The University of Queensland Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Latz","sequence":"additional","affiliation":[{"name":"Institute of Innate Immunity University Hospital University of Bonn Bonn Germany"},{"name":"Department of Infectious Diseases and Immunology University of Massachusetts Medical School Worcester MA USA"},{"name":"German Center for Neurodegenerative Diseases Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Mansell","sequence":"additional","affiliation":[{"name":"Centre for Innate Immunity and Infectious Diseases MIMR\u2010PHI Institute of Medical Research Clayton Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C G","family":"Sobey","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Monash University Clayton Vic. Australia"},{"name":"Department of Surgery Monash Medical Centre Southern Clinical School Monash University Clayton Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G R","family":"Drummond","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Monash University Clayton Vic. Australia"},{"name":"Department of Surgery Monash Medical Centre Southern Clinical School Monash University Clayton Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,7,31]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12449"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12451"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellbi.2007.03.036"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3109\/08037051.2014.940710"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1100613"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901363"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jhh.1001785"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.37.2.781"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2003.00929.x"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000221716.55088.d4"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M707692200"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.112.201251"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-9-260"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3806"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2143(97)90178-5"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V87.6.2095.bloodjournal8762095"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.1999.0837"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08938"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00466.2007"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.300.8.924"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.1467.288"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1636"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.110.163576"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1631"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.151.5.7735624"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.11.7611"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00872.x"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.25.5.1111"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12876"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003597"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2009.12.004"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2013.11.005"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00708.2005"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.109.145094"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00098.2009"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02664"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04515"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04516"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00258.2014"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1161\/hy1101.092839"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00873.x"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2005.10.030"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.090074"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1161\/hy09t1.094234"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1012543"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2013.07.009"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002843"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201698"},{"key":"e_1_2_10_50_1","first-page":"15","article-title":"Targeting the NLRP3 inflammasome in chronic inflammatory diseases: current perspectives","volume":"8","author":"Ozaki E","year":"2015","journal-title":"J Inflamm Res"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1143"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpcardio1453"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2011.06.012"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/hr.2010.148"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2011.05482.x"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-013-0398-z"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.73"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.040"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1184003"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.08.001"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2261-2-3"},{"key":"e_1_2_10_62_1","first-page":"e1","article-title":"Renin\u2010dependent hypertension in mice requires the NLRP3\u2010inflammasome","volume":"3","author":"Wang AQ","year":"2014","journal-title":"J Hypertens"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0114895"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2228"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.2.742"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.111.173328"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbph.13230","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.13230","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T18:37:13Z","timestamp":1694543833000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.13230"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7,31]]},"references-count":65,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2016,2]]}},"alternative-id":["10.1111\/bph.13230"],"URL":"https:\/\/doi.org\/10.1111\/bph.13230","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7,31]]},"assertion":[{"value":"2015-01-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-06-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-07-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}