Over-expression of Roquin aggravates T cell mediated hepatitis in transgenic mice using T cell specific promoter.
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.
['Ji|Young Rae|YR|', 'Kim|Hei Jung|HJ|', 'Yu|Dong Hun|DH|', 'Bae|Ki Beom|KB|', 'Park|Seo Jin|SJ|', 'Park|Si Jun|SJ|', 'Jang|Woo Young|WY|', 'Kang|Min-Cheol|MC|', 'Jeong|Jain|J|', 'Sung|Yong Hun|YH|', 'Choi|Minjee|M|', 'Park|Taejun|T|', 'Park|Taesun|T|', 'Yun|Jong Won|JW|', 'Lee|Hyun-Shik|HS|', 'Lee|Sanggyu|S|', 'Kim|Myoung Ok|MO|', 'Ryoo|Zae Young|ZY|']
D000818:Animals D017209:Apoptosis D056486:Chemical and Drug Induced Liver Injury D003208:Concanavalin A D005260:Female D005786:Gene Expression Regulation D022781:Hepatocytes D007371:Interferon-gamma D015850:Interleukin-6 D008213:Lymphocyte Activation D018655:Lymphocyte Count D051379:Mice D008822:Mice, Transgenic D011401:Promoter Regions, Genetic D019253:Proto-Oncogene Proteins c-bcl-2 D050791:STAT Transcription Factors D015398:Signal Transduction D050378:T-Lymphocytes, Regulatory D058504:Th17 Cells D014409:Tumor Necrosis Factor-alpha D044767:Ubiquitin-Protein Ligases
Roquin Hepatitis Transgenic mice Concanavalin A T cell activation