{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:01:31Z","timestamp":1791212491932,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2012,4,6]],"date-time":"2012-04-06T00:00:00Z","timestamp":1333670400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Alcoholism Clin &amp; Exp Res"],"published-print":{"date-parts":[[2012,11]]},"abstract":"\n Background<\/jats:title>\n \n During the course of alcohol\u2010induced liver damage, hepatic stellate cells are transformed into proliferative, fibrogenic, and contractile myofibroblasts. Aryl hydrocarbon receptor (\n A<\/jats:styled-content>\n h\n R<\/jats:styled-content>\n ) is a transcription factor that controls the expression of genes involved in the metabolism of xenobiotics, inflammation, cell proliferation, and death.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Immortal mouse hepatic stellate cells (\n MHSC<\/jats:styled-content>\n s) were isolated from transgenic mice that expressed a thermolabile\n SV<\/jats:styled-content>\n 40 tumor antigen. Quantitative real\u2010time reverse transcription polymerase chain reaction assays, Western blot analysis, promoter activity assays, and chromatin immunoprecipitation analyses were performed for studying the effect of ethanol (\n E<\/jats:styled-content>\n t\n OH<\/jats:styled-content>\n ) on AhR expression and transcriptional activity.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Treatment of MHSCs with 50 to 200\u00a0mM\n E<\/jats:styled-content>\n t\n OH<\/jats:styled-content>\n for 6\u00a0hours induced AhR nuclear translocation, enhanced the promoter activity of cytochrome P450 (\n CYP<\/jats:styled-content>\n ) 1A1, increased the amount of AhR bound to the promoter of\n CYP1A1<\/jats:styled-content>\n and 1\n B<\/jats:styled-content>\n 1, and up\u2010regulated the m\n RNA<\/jats:styled-content>\n expression of these AhR target genes in a dose\u2010dependent manner. In contrast,\n E<\/jats:styled-content>\n t\n OH<\/jats:styled-content>\n exposure down\u2010regulated AhR m\n RNA<\/jats:styled-content>\n and protein expression. Similarly, benzo(a)pyrene (\n B<\/jats:styled-content>\n a\n P<\/jats:styled-content>\n ) at 10\u00a0nM reduced\n A<\/jats:styled-content>\n h\n R<\/jats:styled-content>\n and increased\n CYP<\/jats:styled-content>\n 1\n A<\/jats:styled-content>\n 1 and 1\n B<\/jats:styled-content>\n 1 m\n RNA<\/jats:styled-content>\n s. Pretreatment of\n MHSC<\/jats:styled-content>\n s with 50\u00a0mM\n E<\/jats:styled-content>\n t\n OH<\/jats:styled-content>\n for 7\u00a0days diminished the capacity of\n MHSC<\/jats:styled-content>\n s to express\n CYP<\/jats:styled-content>\n 1\n A<\/jats:styled-content>\n 1 and 1\n B<\/jats:styled-content>\n 1 induced by a 200\u00a0mM\n E<\/jats:styled-content>\n t\n OH<\/jats:styled-content>\n challenge, or by 10\u00a0nM\n B<\/jats:styled-content>\n a\n P<\/jats:styled-content>\n . However, the up\u2010regulatory effect of\n E<\/jats:styled-content>\n t\n OH<\/jats:styled-content>\n on solute carrier family 16, member 6 (SLC16a6) was unaffected by\n E<\/jats:styled-content>\n t\n OH<\/jats:styled-content>\n pretreatment. Similar to\n E<\/jats:styled-content>\n t\n OH<\/jats:styled-content>\n , dimethyl sulfoxide (\n DMSO<\/jats:styled-content>\n ) at concentrations of 50 to 100\u00a0mM down\u2010regulated\n A<\/jats:styled-content>\n h\n R<\/jats:styled-content>\n and up\u2010regulated\n CYP<\/jats:styled-content>\n 1\n A<\/jats:styled-content>\n 1 m\n RNA<\/jats:styled-content>\n expression in a dose\u2010dependent manner.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n These data, for the first time, demonstrate that\n E<\/jats:styled-content>\n t\n OH<\/jats:styled-content>\n activates\n MHSC<\/jats:styled-content>\n AhR and down\u2010regulates its expression. Chronic\n E<\/jats:styled-content>\n t\n OH<\/jats:styled-content>\n pretreatment lowers the availability of AhR, and specifically diminishes the inducibility of\n CYP<\/jats:styled-content>\n genes. The effect on AhR appears to not be an\n E<\/jats:styled-content>\n t\n OH<\/jats:styled-content>\n \u2010specific response, as\n DMSO<\/jats:styled-content>\n alone (and possibly other organic solvents) was also able to activate\n A<\/jats:styled-content>\n h\n R<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/j.1530-0277.2012.01787.x","type":"journal-article","created":{"date-parts":[[2012,4,6]],"date-time":"2012-04-06T14:16:55Z","timestamp":1333721815000},"page":"1873-1881","source":"Crossref","is-referenced-by-count":27,"title":["Regulation of the Activity and Expression of Aryl Hydrocarbon Receptor by Ethanol in Mouse Hepatic Stellate Cells"],"prefix":"10.1111","volume":"36","author":[{"given":"Hong Feng","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Physiology Meharry Medical College Nashville Tennessee"},{"name":"Wuhan University School of Basic Medical Science Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing Hua","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Physiology Meharry Medical College Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Physiology Meharry Medical College Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li Chun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Physiology Meharry Medical College Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang Lin","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Physiology Meharry Medical College Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joey V.","family":"Barnett","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Vanderbilt University Medical Center Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong Mao","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Physiology Meharry Medical College Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,4,6]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"3155","article-title":"Alcohol consumption and cigarette smoking increase the frequency of p53 mutations in non\u2010small cell lung cancer","volume":"60","author":"Ahrendt SA","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/agp005"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/21.11.2123"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.alc.0000189284.98684.22"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.40.28708"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.2000.279.1.G100"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.08.162"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.35.040195.001515"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.15288\/jsa.2005.66.130"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.12.5096"},{"key":"e_1_2_6_12_1","first-page":"5098","article-title":"Functional analysis of the transcriptional promoter for the CYP1A1 gene","volume":"10","author":"Jones KW","year":"1990","journal-title":"Mol Cell Biol"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004410050594"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a116433"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-95-2-139"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.10784"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/03602530600632063"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2009.08.001"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2011.04.020"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1976.03270150034027"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.12.8432"},{"key":"e_1_2_6_22_1","first-page":"5","article-title":"Exploring alcohol's effects on liver function","volume":"21","author":"Maher JJ","year":"1997","journal-title":"Alcohol Health Res World"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.02.005"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M404315200"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.20656"},{"key":"e_1_2_6_26_1","first-page":"367","article-title":"Severity of liver injury in experimental alcoholic liver disease. 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