Cyclosporine suppresses cell growth and collagen production in hepatic stellate cells

M. Nakamuta, Motoyuki Kohjima, M. Fukushima, S. Morizono, K. Kotoh, N. Kobayashi, M. Enjoji

研究成果: ジャーナルへの寄稿記事

14 引用 (Scopus)

抄録

Background. In HCV-related graft hepatitis, immunosuppression has been implicated in rapid progression to cirrhosis, a serious clinical issue. We investigated the effects of cyclosporine or tacrolimus on cell growth and collagen production by hepatic stellate cells (HSC), which play a role in hepatic fibrosis. Materials and methods. Cultured rat HSCs and human HSC-derived TWNT-4 cells were evaluated for proliferation, type I collagen, phosphorylation states of mitogen-activated protein kinases extracellular signal-regulated kinase 1/2; [MAPKs Erk1/2], c-Jun N-terminal kinase (JNK, p38), as well as the expression of collagen, matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) genes. Results. Cyclosporine suppressed cell growth and collagen production in a concentration-dependent manner. At clinically relevant concentrations of 0.125 μmol (150 ng/mL) cyclosporine significantly reduced collagen production per cell by more than 50%. Similarly, tacrolimus also reduced both collagen concentration and cell number; however, tacrolimus at a clinically relevant concentration of 12.5 nmol (10 ng/mL) did not significantly reduce collagen production. Treatment with cyclosporine reduced type I collagen and TIMP-1 expression and enhanced MMP-1 expression. Cyclosporine also inhibited phosphorylation strongly for JNK and p38, and weakly inhibited for Erk1/2. Conclusion. These findings demonstrated that cyclosporine suppresses cell growth and collagen production, suggesting that it may have an antifibrogenic effect.

元の言語英語
ページ(範囲)4598-4602
ページ数5
ジャーナルTransplantation Proceedings
37
発行部数10
DOI
出版物ステータス出版済み - 12 1 2005

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Hepatic Stellate Cells
Cyclosporine
Collagen
Matrix Metalloproteinase 1
Growth
Tacrolimus
Tissue Inhibitor of Metalloproteinase-1
Collagen Type I
Fibrosis
Phosphorylation
Matrix Metalloproteinase Inhibitors
Mitogen-Activated Protein Kinase 3
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinases
Immunosuppression
Hepatitis
Cell Count
Transplants
Liver

All Science Journal Classification (ASJC) codes

  • Surgery
  • Transplantation

これを引用

Cyclosporine suppresses cell growth and collagen production in hepatic stellate cells. / Nakamuta, M.; Kohjima, Motoyuki; Fukushima, M.; Morizono, S.; Kotoh, K.; Kobayashi, N.; Enjoji, M.

:: Transplantation Proceedings, 巻 37, 番号 10, 01.12.2005, p. 4598-4602.

研究成果: ジャーナルへの寄稿記事

Nakamuta, M, Kohjima, M, Fukushima, M, Morizono, S, Kotoh, K, Kobayashi, N & Enjoji, M 2005, 'Cyclosporine suppresses cell growth and collagen production in hepatic stellate cells', Transplantation Proceedings, 巻. 37, 番号 10, pp. 4598-4602. https://doi.org/10.1016/j.transproceed.2005.10.104
Nakamuta, M. ; Kohjima, Motoyuki ; Fukushima, M. ; Morizono, S. ; Kotoh, K. ; Kobayashi, N. ; Enjoji, M. / Cyclosporine suppresses cell growth and collagen production in hepatic stellate cells. :: Transplantation Proceedings. 2005 ; 巻 37, 番号 10. pp. 4598-4602.
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abstract = "Background. In HCV-related graft hepatitis, immunosuppression has been implicated in rapid progression to cirrhosis, a serious clinical issue. We investigated the effects of cyclosporine or tacrolimus on cell growth and collagen production by hepatic stellate cells (HSC), which play a role in hepatic fibrosis. Materials and methods. Cultured rat HSCs and human HSC-derived TWNT-4 cells were evaluated for proliferation, type I collagen, phosphorylation states of mitogen-activated protein kinases extracellular signal-regulated kinase 1/2; [MAPKs Erk1/2], c-Jun N-terminal kinase (JNK, p38), as well as the expression of collagen, matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) genes. Results. Cyclosporine suppressed cell growth and collagen production in a concentration-dependent manner. At clinically relevant concentrations of 0.125 μmol (150 ng/mL) cyclosporine significantly reduced collagen production per cell by more than 50{\%}. Similarly, tacrolimus also reduced both collagen concentration and cell number; however, tacrolimus at a clinically relevant concentration of 12.5 nmol (10 ng/mL) did not significantly reduce collagen production. Treatment with cyclosporine reduced type I collagen and TIMP-1 expression and enhanced MMP-1 expression. Cyclosporine also inhibited phosphorylation strongly for JNK and p38, and weakly inhibited for Erk1/2. Conclusion. These findings demonstrated that cyclosporine suppresses cell growth and collagen production, suggesting that it may have an antifibrogenic effect.",
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AU - Enjoji, M.

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N2 - Background. In HCV-related graft hepatitis, immunosuppression has been implicated in rapid progression to cirrhosis, a serious clinical issue. We investigated the effects of cyclosporine or tacrolimus on cell growth and collagen production by hepatic stellate cells (HSC), which play a role in hepatic fibrosis. Materials and methods. Cultured rat HSCs and human HSC-derived TWNT-4 cells were evaluated for proliferation, type I collagen, phosphorylation states of mitogen-activated protein kinases extracellular signal-regulated kinase 1/2; [MAPKs Erk1/2], c-Jun N-terminal kinase (JNK, p38), as well as the expression of collagen, matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) genes. Results. Cyclosporine suppressed cell growth and collagen production in a concentration-dependent manner. At clinically relevant concentrations of 0.125 μmol (150 ng/mL) cyclosporine significantly reduced collagen production per cell by more than 50%. Similarly, tacrolimus also reduced both collagen concentration and cell number; however, tacrolimus at a clinically relevant concentration of 12.5 nmol (10 ng/mL) did not significantly reduce collagen production. Treatment with cyclosporine reduced type I collagen and TIMP-1 expression and enhanced MMP-1 expression. Cyclosporine also inhibited phosphorylation strongly for JNK and p38, and weakly inhibited for Erk1/2. Conclusion. These findings demonstrated that cyclosporine suppresses cell growth and collagen production, suggesting that it may have an antifibrogenic effect.

AB - Background. In HCV-related graft hepatitis, immunosuppression has been implicated in rapid progression to cirrhosis, a serious clinical issue. We investigated the effects of cyclosporine or tacrolimus on cell growth and collagen production by hepatic stellate cells (HSC), which play a role in hepatic fibrosis. Materials and methods. Cultured rat HSCs and human HSC-derived TWNT-4 cells were evaluated for proliferation, type I collagen, phosphorylation states of mitogen-activated protein kinases extracellular signal-regulated kinase 1/2; [MAPKs Erk1/2], c-Jun N-terminal kinase (JNK, p38), as well as the expression of collagen, matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) genes. Results. Cyclosporine suppressed cell growth and collagen production in a concentration-dependent manner. At clinically relevant concentrations of 0.125 μmol (150 ng/mL) cyclosporine significantly reduced collagen production per cell by more than 50%. Similarly, tacrolimus also reduced both collagen concentration and cell number; however, tacrolimus at a clinically relevant concentration of 12.5 nmol (10 ng/mL) did not significantly reduce collagen production. Treatment with cyclosporine reduced type I collagen and TIMP-1 expression and enhanced MMP-1 expression. Cyclosporine also inhibited phosphorylation strongly for JNK and p38, and weakly inhibited for Erk1/2. Conclusion. These findings demonstrated that cyclosporine suppresses cell growth and collagen production, suggesting that it may have an antifibrogenic effect.

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