{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T02:47:36Z","timestamp":1788922056318,"version":"build-2803163510"},"reference-count":41,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T00:00:00Z","timestamp":1658966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Agriculture, Food and Rural Affairs","award":["122001021SB01061382116530000"],"award-info":[{"award-number":["122001021SB01061382116530000"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Simvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl CoA reductase and has been found to have protective effects against several bacterial infections. In this study, we investigate the effects of simvastatin treatment on RAW 264.7 macrophage cells and ICR mice against Brucella (B.) abortus infections. The invasion assay revealed that simvastatin inhibited the Brucella invasion into macrophage cells by blocking the mevalonic pathway. The treatment of simvastatin enhanced the trafficking of Toll-like receptor 4 in membrane lipid raft microdomains, accompanied by the increased phosphorylation of its downstream signaling pathways, including JAK2 and MAPKs, upon =Brucella infection. Notably, the suppressive effect of simvastatin treatment on Brucella invasion was not dependent on the reduction of cholesterol synthesis but probably on the decline of farnesyl pyrophosphate and geranylgeranyl pyrophosphate synthesis. In addition to a direct brucellacidal ability, simvastatin administration showed increased cytokine TNF-\u03b1 and differentiation of CD8+ T cells, accompanied by reduced bacterial survival in spleens of ICR mice. These data suggested the involvement of the mevalonate pathway in the phagocytosis of B. abortus into RAW 264.7 macrophage cells and the regulation of simvastatin on the host immune system against Brucella infections. Therefore, simvastatin is a potential candidate for studying alternative therapy against animal brucellosis.<\/jats:p>","DOI":"10.3390\/ijms23158337","type":"journal-article","created":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T20:49:28Z","timestamp":1659041368000},"page":"8337","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Simvastatin Inhibits Brucella abortus Invasion into RAW 264.7 Cells through Suppression of the Mevalonate Pathway and Promotes Host Immunity during Infection in a Mouse Model"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1903-7885","authenticated-orcid":false,"given":"Trang Thi","family":"Nguyen","sequence":"first","affiliation":[{"name":"Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heejin","family":"Kim","sequence":"additional","affiliation":[{"name":"Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7065-7276","authenticated-orcid":false,"given":"Tran Xuan Ngoc","family":"Huy","sequence":"additional","affiliation":[{"name":"Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Korea"},{"name":"Institute of Applied Sciences, HUTECH University, 475A Dien Bien Phu St., Ward 25, Binh Thanh District, Ho Chi Minh City 72300, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2437-7366","authenticated-orcid":false,"given":"Wongi","family":"Min","sequence":"additional","affiliation":[{"name":"Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7552-6416","authenticated-orcid":false,"given":"Hujang","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisha Wehdnesday Bernardo","family":"Reyes","sequence":"additional","affiliation":[{"name":"Department of Veterinary Paraclinical Sciences, College of Veterinary Medicine, University of the Philippines Los Ba\u00f1os, Los Ba\u00f1os 4031, Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnhwa","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Chonbuk National University, Iksan 54596, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5795-2019","authenticated-orcid":false,"given":"Suk","family":"Kim","sequence":"additional","affiliation":[{"name":"Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.vetmic.2009.06.021","article-title":"Brucellosis: A re-emerging zoonosis","volume":"140","author":"Seleem","year":"2010","journal-title":"Vet. 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