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

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T-cells
Liver
Transgenic Mice
Hepatitis
Concanavalin A
T-Lymphocytes
Wounds and Injuries
Liver Neoplasms
Infiltration
Apoptosis
Th17 Cells
Ubiquitin-Protein Ligases
In Situ Nick-End Labeling
Regulatory T-Lymphocytes
Chronic Hepatitis
Interleukin-6
Cell Count
Staining and Labeling
Cytokines
Chemical activation

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Ji, Young Rae ; Kim, Hei Jung ; Yu, Dong Hun ; Bae, Ki Beom ; Park, Seo Jin ; Park, Si Jun ; Jang, Woo Young ; Kang, Min Cheol ; Jeong, Jain ; Sung, Yong Hun ; Choi, Minjee ; Park, Taejun ; Park, Taesun ; Yun, Jong Won ; Lee, Hyun Shik ; Lee, Sanggyu ; Kim, Myoung Ok ; Ryoo, Zae Young. / Over-expression of Roquin aggravates T cell mediated hepatitis in transgenic mice using T cell specific promoter. In: Biochemical and Biophysical Research Communications. 2014 ; Vol. 452, No. 3. pp. 822-827.
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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.",
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Ji, YR, Kim, HJ, Yu, DH, Bae, KB, Park, SJ, Park, SJ, Jang, WY, Kang, MC, Jeong, J, Sung, YH, Choi, M, Park, T, Park, T, Yun, JW, Lee, HS, Lee, S, Kim, MO & Ryoo, ZY 2014, 'Over-expression of Roquin aggravates T cell mediated hepatitis in transgenic mice using T cell specific promoter', Biochemical and Biophysical Research Communications, vol. 452, no. 3, pp. 822-827. https://doi.org/10.1016/j.bbrc.2014.09.001

Over-expression of Roquin aggravates T cell mediated hepatitis in transgenic mice using T cell specific promoter. / Ji, Young Rae; Kim, Hei Jung; Yu, Dong Hun; Bae, Ki Beom; Park, Seo Jin; Park, Si Jun; Jang, Woo Young; Kang, Min Cheol; Jeong, Jain; Sung, Yong Hun; Choi, Minjee; Park, Taejun; Park, Taesun; Yun, Jong Won; Lee, Hyun Shik; Lee, Sanggyu; Kim, Myoung Ok; Ryoo, Zae Young.

In: Biochemical and Biophysical Research Communications, Vol. 452, No. 3, 26.09.2014, p. 822-827.

Research output: Contribution to journalArticle

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T1 - Over-expression of Roquin aggravates T cell mediated hepatitis in transgenic mice using T cell specific promoter

AU - Ji, Young Rae

AU - Kim, Hei Jung

AU - Yu, Dong Hun

AU - Bae, Ki Beom

AU - Park, Seo Jin

AU - Park, Si Jun

AU - Jang, Woo Young

AU - Kang, Min Cheol

AU - Jeong, Jain

AU - Sung, Yong Hun

AU - Choi, Minjee

AU - Park, Taejun

AU - Park, Taesun

AU - Yun, Jong Won

AU - Lee, Hyun Shik

AU - Lee, Sanggyu

AU - Kim, Myoung Ok

AU - Ryoo, Zae Young

PY - 2014/9/26

Y1 - 2014/9/26

N2 - 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.

AB - 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.

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