Cyclosporine suppresses cell growth and collagen production in hepatic stellate cells

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

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4598-4602
Number of pages5
JournalTransplantation Proceedings
Volume37
Issue number10
DOIs
Publication statusPublished - Dec 1 2005

All Science Journal Classification (ASJC) codes

  • Surgery
  • Transplantation

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