{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:21:35Z","timestamp":1790173295284,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T00:00:00Z","timestamp":1586908800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:p>In organ transplantation, donor\u2010specific HLA antibody (DSA) is considered a major cause of graft rejection. Because DSA targets primarily donor\u2010specific human leukocyte antigen (HLA) expressed on graft endothelial cells, the prevention of its expression is a possible strategy for avoiding or salvaging DSA\u2010mediated graft rejection. We examined the effect of various clinically used drugs on HLA class II expression on endothelial cells. Interferon\u2010\u03b3 (IFN\u2010\u03b3)\u2010induced HLA class II DR (HLA\u2010DR) was downregulated by everolimus (EVR, 49.1%\u00a0\u00b1\u00a00.8%; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) and fluvastatin (FLU, 33.8%\u00a0\u00b1\u00a00.6%; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01). Moreover, the combination of EVR and FLU showed a greater suppressive effect on HLA\u2010DR expression. In contrast, cyclosporine, tacrolimus, mycophenolic acid, and prednisolone did not exhibit any significant suppressive effect. FLU, but not EVR, suppressed mRNA of HLA\u2010DR. Imaging analysis revealed that HLA\u2010DR expressed in cytosol or on the cell surface was repressed by EVR (cytosol: 58.6%\u00a0\u00b1\u00a04.9%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01; cell surface: 80.9%\u00a0\u00b1\u00a04.0%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) and FLU (cytosol: 19.0%\u00a0\u00b1\u00a03.4%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01; cell surface: 48.3%\u00a0\u00b1\u00a04.8%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01). These data indicated that FLU and EVR suppressed IFN\u2010\u03b3\u2010induced HLA\u2010DR expression at the transcriptional and post\u2010translational level, respectively, suggesting a potential approach for alleviating DSA\u2010related issues in organ transplantation.<\/jats:p>","DOI":"10.1002\/2211-5463.12854","type":"journal-article","created":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T03:45:40Z","timestamp":1585712740000},"page":"927-936","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Interferon\u2010\u03b3\u2010induced HLA Class II expression on endothelial cells is decreased by inhibition of mTOR and HMG\u2010CoA reductase"],"prefix":"10.1002","volume":"10","author":[{"given":"Akihiro","family":"Maenaka","sequence":"first","affiliation":[{"name":"Department of Pharmacy Aichi Medical University School of Medicine Nagakute Japan"},{"name":"Department of Renal Transplant Surgery Aichi Medical University School of Medicine Nagakute Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3229-5192","authenticated-orcid":false,"given":"Iwasaki","family":"Kenta","sequence":"additional","affiliation":[{"name":"Department of Kidney Disease and Transplant Immunology Aichi Medical University School of Medicine Nagakute Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6296-2921","authenticated-orcid":false,"given":"Akinobu","family":"Ota","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Aichi Medical University School of Medicine Nagakute Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Miwa","sequence":"additional","affiliation":[{"name":"Department of Kidney Disease and Transplant Immunology Aichi Medical University School of Medicine Nagakute Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Ohashi","sequence":"additional","affiliation":[{"name":"Division of Biostatistics Clinical Research Center Aichi Medical University School of Medicine Nagakute Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosei","family":"Horimi","sequence":"additional","affiliation":[{"name":"Department of Renal Transplant Surgery Aichi Medical University School of Medicine Nagakute Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Matsuoka","sequence":"additional","affiliation":[{"name":"Department of Renal Transplant Surgery Aichi Medical University School of Medicine Nagakute Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Ohnishi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Aichi Medical University School of Medicine Nagakute Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuharu","family":"Uchida","sequence":"additional","affiliation":[{"name":"Department of Kidney Disease and Transplant Immunology Aichi Medical University School of Medicine Nagakute Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaaki","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Renal Transplant Surgery Aichi Medical University School of Medicine Nagakute Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,4,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.TP.0000055833.65192.3B"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0012.2012.01654.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e31817c4cb8"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/tan.13111"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2010.10.018"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000001012"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.10.2851"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000314547"},{"issue":"3","key":"e_1_2_9_10_1","first-page":"1","article-title":"KDIGO clinical practice guideline for the care of kidney transplant recipients","volume":"9","author":"Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group","year":"2009","journal-title":"Am J Transplant"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200203270-00016"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.738"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-200124100-00004"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.12589"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12219"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000001924"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e3182424df3"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000002049"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trre.2017.01.002"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12882-018-1057-4"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trim.2016.12.004"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2018010009"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.14186"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13132"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.15480"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02548"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxs155"},{"key":"e_1_2_9_28_1","first-page":"785","article-title":"Cellular misfolded proteins transported to the cell surface by MHC class II molecules are targeted by autoantibodies","volume":"87","author":"Arase H","year":"2015","journal-title":"Seikagaku"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI120391"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.2000.01251.x"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(93)90166-7"},{"key":"e_1_2_9_32_1","first-page":"496","article-title":"Dyslipidaemia among renal transplant recipients: cyclosporine versus tacrolimus","volume":"64","author":"Fazal MA","year":"2014","journal-title":"J Pak Med Assoc"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2019.01.011"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/82219"},{"key":"e_1_2_9_35_1","first-page":"41","article-title":"The HMG\u2010CoA reductase inhibitor simvastatin inhibits IFN\u2010gamma induced MHC class II expression in human vascular endothelial cells","volume":"131","author":"Kwak B","year":"2001","journal-title":"Swiss Med Wkly"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0012.2005.00326.x"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1053-2498(02)01221-4"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.5414\/CPP44163"}],"container-title":["FEBS Open Bio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2F2211-5463.12854","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/2211-5463.12854","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/2211-5463.12854","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/2211-5463.12854","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T04:19:06Z","timestamp":1694060346000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1002\/2211-5463.12854"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,15]]},"references-count":37,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,5]]}},"alternative-id":["10.1002\/2211-5463.12854"],"URL":"https:\/\/doi.org\/10.1002\/2211-5463.12854","archive":["Portico"],"relation":{},"ISSN":["2211-5463","2211-5463"],"issn-type":[{"value":"2211-5463","type":"print"},{"value":"2211-5463","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,15]]},"assertion":[{"value":"2019-12-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}