Over-expression of Roquin aggravates T cell mediated hepatitis in transgenic mice using T cell specific promoter

Young Rae Ji, Hei Jung Kim, Dong Hun Yu, Ki Beom Bae, Seo Jin Park, Si Jun Park, Woo Young Jang, Min Cheol Kang, Jain Jeong, Yong Hun Sung, Minjee Choi, Taejun Park, Taesun Park, Jong Won Yun, Hyun Shik Lee, Sanggyu Lee, Myoung Ok Kim, Zae Young Ryoo

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)822-827
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume452
Issue number3
DOIs
Publication statusPublished - 2014 Sep 26

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Ji, Y. R., Kim, H. J., Yu, D. H., Bae, K. B., Park, S. J., Park, S. J., Jang, W. Y., Kang, M. C., Jeong, J., Sung, Y. H., Choi, M., Park, T., Park, T., Yun, J. W., Lee, H. S., Lee, S., Kim, M. O., & Ryoo, Z. Y. (2014). Over-expression of Roquin aggravates T cell mediated hepatitis in transgenic mice using T cell specific promoter. Biochemical and Biophysical Research Communications, 452(3), 822-827. https://doi.org/10.1016/j.bbrc.2014.09.001