{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:11:43Z","timestamp":1790518303343,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,9,8]],"date-time":"2020-09-08T00:00:00Z","timestamp":1599523200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The blood\u2013brain barrier (BBB) is a highly selective membrane composed predominantly of brain capillary endothelial cells expressing drug efflux transporters that prevent substrates from accessing the brain. Inflammation is associated with central nervous system diseases and can impair BBB permeability via several mechanisms, including altered transporter and cell junction expression. This can modify the brain\u2019s exposure to drugs. However, comprehensive genomic analysis of the impact of interleukin (IL)\u20106, which plays a key role in the inflammatory response, on the BBB is lacking. In the present study, we analyzed the effects of exposure of hCMEC\/D3 cells to 20\u00a0ng\/mL IL\u20106 for 72\u00a0h. We performed RNA sequencing and ABC transporter efflux assays. Physiologically based pharmacokinetics (PBPK) simulations were conducted to evaluate the potential impact of IL\u20106 on the digoxin pharmacokinetics profile and brain exposure by decreasing BBB ABCB1 efflux activity. Exposure of hCMEC\/D3 cells to IL\u20106 triggered the deregulation of numerous genes involved in barrier permeability, such as cell junctions, focal adherens complex, and cell adhesion molecules. We observed mild modification of the mRNA expression and efflux activities of ABC transporters. PBPK simulation showed that, if we only consider the impact of IL\u20106 on ABCB1 transporter, the modification of the digoxin pharmacokinetics profile and brain exposure is slight. IL\u20106 slightly affected the gene expression levels and activities of ABC transporters on BBB cells, exhibiting a weaker effect than on hepatic cells. However, inflammation may cause other modifications, such as altered BBB permeability, that could modify drug pharmacokinetics.<\/jats:p>","DOI":"10.1111\/fcp.12596","type":"journal-article","created":{"date-parts":[[2020,8,5]],"date-time":"2020-08-05T20:24:18Z","timestamp":1596659058000},"page":"397-409","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Impact of interleukin\u20106 on drug transporters and permeability in the hCMEC\/D3 blood\u2013brain barrier model"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3731-3014","authenticated-orcid":false,"given":"Florian","family":"Simon","sequence":"first","affiliation":[{"name":"EA3738 Facult\u00e9 de m\u00e9decine de Lyon\u2010Sud Universit\u00e9 de Lyon 1 165 chemin du Grand Revoyet, Facult\u00e9 de m\u00e9decine et ma\u00efeutique Oullins France 69921 France"},{"name":"Laboratoire de Biochimie\u2010Toxicologie Centre Hospitalier Lyon\u2010Sud Hospices civils de Lyon 165 chemin du Grand Revoyet Pierre\u2010B\u00e9nite France 69310 France"},{"name":"Institut de Recherches Internationales Servier Direction of Clinical PK and Pharmacometrics 50 rue Carnot Suresnes 92150 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laetitia","family":"Guyot","sequence":"additional","affiliation":[{"name":"Laboratoire de Biochimie\u2010Toxicologie Centre Hospitalier Lyon\u2010Sud Hospices civils de Lyon 165 chemin du Grand Revoyet Pierre\u2010B\u00e9nite France 69310 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Garcia","sequence":"additional","affiliation":[{"name":"Laboratoire de Biochimie\u2010Toxicologie Centre Hospitalier Lyon\u2010Sud Hospices civils de Lyon 165 chemin du Grand Revoyet Pierre\u2010B\u00e9nite France 69310 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaelle","family":"Vilchez","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon Department of Biostatistics 162 avenue Lacassagne Lyon 69424 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Bardel","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon Department of Biostatistics 162 avenue Lacassagne Lyon 69424 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marylore","family":"Chenel","sequence":"additional","affiliation":[{"name":"Institut de Recherches Internationales Servier Direction of Clinical PK and Pharmacometrics 50 rue Carnot Suresnes 92150 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Tod","sequence":"additional","affiliation":[{"name":"EA3738 Facult\u00e9 de m\u00e9decine de Lyon\u2010Sud Universit\u00e9 de Lyon 1 165 chemin du Grand Revoyet, Facult\u00e9 de m\u00e9decine et ma\u00efeutique Oullins France 69921 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e9a","family":"Payen","sequence":"additional","affiliation":[{"name":"Laboratoire de Biochimie\u2010Toxicologie Centre Hospitalier Lyon\u2010Sud Hospices civils de Lyon 165 chemin du Grand Revoyet Pierre\u2010B\u00e9nite France 69310 France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05730.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2008.11.001"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2012.03702.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2016.03.010"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-009-9431-1"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-5728(95)00148-4"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705227"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000026391"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-1091"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCO.0b013e32833cf3bc"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.114.060962"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.108.023630"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-018-0614-2"},{"key":"e_1_2_7_15_1","unstructured":"KleinM.Role of inflammatory cytokine signaling in the regulation of detoxifying functions in human hepatocytes and liver. Stuttgart University 2014."},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-3458fje"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2016.04.004"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12134"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.23266"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dmpk.2016.03.005"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-019-0395-x"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics8020012"},{"key":"e_1_2_7_23_1","first-page":"149","article-title":"Flow cytometric assessment of P\u2010glycoprotein and multidrug resistance\u2010associated protein activity and expression in canine lymphoma","volume":"29","author":"Pozniak B.","year":"2015","journal-title":"Vivo."},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(92)91593-F"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12343"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1103460"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-7580.2002.00057.x"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(02)00128-4"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2020.146647"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.28575"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2013.02.010"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1006\/cyto.1998.0398"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1080\/09629359890875"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/2045-8118-10-27"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2004.04.018"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(99)00120-4"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01811"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2018.07.030"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.26967"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(01)00242-9"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0894-0959.2004.17603.x"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-016-0564-9"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2016.10.020"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.1987.tb05454.x"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-8981(03)00229-8"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.105.097402"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.12793\/tcp.2015.23.2.42"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2002.121829"}],"container-title":["Fundamental &amp; Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Ffcp.12596","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/fcp.12596","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/fcp.12596","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/fcp.12596","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T12:55:17Z","timestamp":1693572917000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/fcp.12596"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,8]]},"references-count":47,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,4]]}},"alternative-id":["10.1111\/fcp.12596"],"URL":"https:\/\/doi.org\/10.1111\/fcp.12596","archive":["Portico"],"relation":{},"ISSN":["0767-3981","1472-8206"],"issn-type":[{"value":"0767-3981","type":"print"},{"value":"1472-8206","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,8]]},"assertion":[{"value":"2020-06-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}