title: Over-expression of Roquin aggravates T cell mediated hepatitis in transgenic mice using T cell specific promoter.
abstract: Chronic hepatitis is a major cause of liver cancer, so earlier treatment of hepatitis might be reducing liver cancer incidence. Hepatitis can be induced in mice by treatment with Concanavalin A (Con A); the resulting liver injury causes significant CD4(+) T cell activation and infiltration. In these T cells, Roquin, a ring-type E3 ubiquitin ligase, is activated. To investigate the role of Roquin, we examined Con A-induced liver injury and T cell infiltration in transgenic (Tg) mice overexpressing Roquin specifically in T cells. In Roquin Tg mice, Con A treatment caused greater increases in both the levels of liver injury enzymes and liver tissue apoptosis, as revealed by TUNEL and H&E staining, than wild type (WT) mice. Further, Roquin Tg mice respond to Con A treatment with greater increases in the T cell population, particularly Th17 cells, though Treg cell counts are lower. Roquin overexpression also enhances increases in pro-inflammatory cytokines, including IFN-γ, TNF-α and IL-6, upon liver injury. Furthermore, Roquin regulates the immune response and apoptosis in Con A induced hepatitis via STATs, Bax and Bcl2. These findings suggest that over-expression of Roquin exacerbates T-cell mediated hepatitis.
authors.affiliation: School of Life Science, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, Buk-ku, Daegu, Republic of Korea.
authors.forename: Young Rae
authors.initials: YR
authors.lastname: Ji
authors.affiliation: School of Life Science, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, Buk-ku, Daegu, Republic of Korea.
authors.forename: Hei Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: School of Life Science, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, Buk-ku, Daegu, Republic of Korea.
authors.forename: Dong Hun
authors.initials: DH
authors.lastname: Yu
authors.affiliation: School of Life Science, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, Buk-ku, Daegu, Republic of Korea.
authors.forename: Ki Beom
authors.initials: KB
authors.lastname: Bae
authors.affiliation: School of Life Science, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, Buk-ku, Daegu, Republic of Korea.
authors.forename: Seo Jin
authors.initials: SJ
authors.lastname: Park
authors.affiliation: School of Life Science, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, Buk-ku, Daegu, Republic of Korea.
authors.forename: Si Jun
authors.initials: SJ
authors.lastname: Park
authors.affiliation: School of Life Science, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, Buk-ku, Daegu, Republic of Korea.
authors.forename: Woo Young
authors.initials: WY
authors.lastname: Jang
authors.affiliation: School of Life Science, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, Buk-ku, Daegu, Republic of Korea.
authors.forename: Min-Cheol
authors.initials: MC
authors.lastname: Kang
authors.affiliation: School of Life Science, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, Buk-ku, Daegu, Republic of Korea.
authors.forename: Jain
authors.initials: J
authors.lastname: Jeong
authors.affiliation: School of Life Science, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, Buk-ku, Daegu, Republic of Korea.
authors.forename: Yong Hun
authors.initials: YH
authors.lastname: Sung
authors.affiliation: School of Life Science, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, Buk-ku, Daegu, Republic of Korea.
authors.forename: Minjee
authors.initials: M
authors.lastname: Choi
authors.affiliation: Department of Biotechnology, Daegu University, Kyungsan, Kyungbuk, Republic of Korea.
authors.forename: Taejun
authors.initials: T
authors.lastname: Park
authors.affiliation: Department of Food and Nutrition, Brain Korea 21 PLUS Project, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea.
authors.forename: Taesun
authors.initials: T
authors.lastname: Park
authors.affiliation: Department of Biotechnology, Daegu University, Kyungsan, Kyungbuk, Republic of Korea.
authors.forename: Jong Won
authors.initials: JW
authors.lastname: Yun
authors.affiliation: School of Life Science, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, Buk-ku, Daegu, Republic of Korea.
authors.forename: Hyun-Shik
authors.initials: HS
authors.lastname: Lee
authors.affiliation: School of Life Science, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, Buk-ku, Daegu, Republic of Korea.
authors.forename: Sanggyu
authors.initials: S
authors.lastname: Lee
authors.affiliation: Departments of Animal Science, Kyungpook National University, Sangju, Republic of Korea.
authors.forename: Myoung Ok
authors.initials: MO
authors.lastname: Kim
authors.affiliation: School of Life Science, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, Buk-ku, Daegu, Republic of Korea. Electronic address: jaewoong64@hanmail.net.
authors.forename: Zae Young
authors.initials: ZY
authors.lastname: Ryoo
mesh_terms: D000818:Animals; D017209:Apoptosis; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003208:Concanavalin A; D005260:Female; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism / Q000473:pathology; D058504:Th17 Cells / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D019253:Proto-Oncogene Proteins c-bcl-2; D050791:STAT Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D007371:Interferon-gamma; C501406:Rc3h1 protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: Concanavalin A; Hepatitis; Roquin; T cell activation; Transgenic mice