Inhibitory effect of human interferon-beta-1a on activated rat and human hepatic stellate cells

被引:11
作者
Rao, Hui-Ying [1 ]
Wei, Lai [1 ]
Wang, Jiang-Hua [1 ]
Fei, Ran [1 ]
Jiang, Dong [1 ]
Zhang, Quan [1 ]
Chen, Hong-Song [1 ]
Cong, Xu [1 ]
机构
[1] Peking Univ, Inst Hepatol, Peoples Hosp, Beijing 100044, Peoples R China
关键词
hepatic stellate cell; interferon-beta; platelet-derived growth factor; transforming growth factor-beta; GROWTH-FACTOR-BETA; LIVER FIBROSIS; HUMAN-DISEASE; TGF-BETA; ALPHA; PROLIFERATION; MECHANISMS; CIRRHOSIS; THERAPY; TARGETS;
D O I
10.1111/j.1440-1746.2010.06264.x
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background and Aims: Hepatic stellate cells (HSC) are the primary cell type mediating hepatic fibrosis. Although known for its antiviral effects, the inhibitory effects of interferon-beta (IFN-beta) on HSC treatment have not yet been established. Methods: Both human and rat activated HSC cell lines were incubated with increasing concentrations of recombinant human IFN-beta 1a (rhIFN-beta 1a) for 24, 48 or 72 h. The effects of rhIFN-beta 1a on alpha-smooth muscle actin (alpha-SMA), collagen types I and III, transforming growth factor-beta 1 (TGF-beta 1), platelet-derived growth factor-BB (PDGF-BB), and mothers against decapentaplegic homolog (Smad4, Smad7) expression in HSC were examined using Western blotting and immunocytochemistry. Proliferation of HSC was evaluated via bromodeoxyuridine assay. Results: rhIFN-beta 1a treatment had a dose-dependent, inhibitory effect on alpha-SMA and collagen type I protein expression. In addition, rhIFN-beta 1a decreased the expression of collagen type III, TGF-beta 1, PDGF-BB and Smad4 protein expression in HSC compared with untreated cells. We also observed increased Smad7 protein expression and decreased proliferation in rhIFN-beta 1a-treated HSC. Conclusions: Our data suggest that rhIFN-beta 1a treatment decreased alpha-SMA and collagen expression and inhibited the activation of HSC through the inhibition of the TGF-beta and PDGF pathways.
引用
收藏
页码:1777 / 1784
页数:8
相关论文
共 30 条
  • [21] Cytokine receptors and signaling in hepatic stellate cells
    Pinzani, M
    Marra, F
    [J]. SEMINARS IN LIVER DISEASE, 2001, 21 (03) : 397 - 416
  • [22] Activation of hepatic stellate cells - A key issue in liver fibrosis
    Reeves, HL
    Friedman, SL
    [J]. FRONTIERS IN BIOSCIENCE-LANDMARK, 2002, 7 : D808 - D826
  • [23] Pharmacokinetics and pharmacodynamics of recombinant human interferon-beta in healthy male volunteers
    Salmon, P
    LeCotonnec, JY
    Galazka, A
    AbdulAhad, A
    Darragh, A
    [J]. JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 1996, 16 (10) : 759 - 764
  • [24] Different effects of rat interferon alpha, beta and gamma on rat hepatic stellate cell proliferation and activation
    Shen, H
    Zhang, M
    Minuk, GY
    Gong, YW
    [J]. BMC CELL BIOLOGY, 2002, 3 (1)
  • [25] Adenovirus-mediated gene transfer of interferon α improves dimethylnitrosamine-induced liver cirrhosis in rat model
    Suzuki, K
    Aoki, K
    Ohnami, S
    Yoshida, K
    Kazui, T
    Kato, N
    Inoue, K
    Kohara, M
    Yoshida, T
    [J]. GENE THERAPY, 2003, 10 (09) : 765 - 773
  • [26] Interferon-β reduces the mouse liver fibrosis induced by repeated administration of concanavalin A via the direct and indirect effects
    Tanabe, Junichi
    Izawa, Akiko
    Takemi, Natsumi
    Miyauchi, Yasushi
    Torii, Yuichi
    Tsuchiyama, Hiromi
    Suzuki, Tomohiko
    Sone, Saburo
    Ando, Kazuki
    [J]. IMMUNOLOGY, 2007, 122 (04) : 562 - 570
  • [27] Identification of novel TGF-β/Smad gene targets in dermal fibroblasts using a combined cDNA microarray/promoter transactivation approach
    Verrecchia, F
    Chu, ML
    Mauviel, A
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (20) : 17058 - 17062
  • [28] Smad4 protein stability is regulated by ubiquitin ligase SCFβ-TrCP1
    Wan, M
    Tang, Y
    Tytler, EM
    Lu, CY
    Jin, BW
    Vickers, SM
    Yang, L
    Shi, XM
    Cao, X
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (15) : 14484 - 14487
  • [29] Human hepatic stellate cell lines, LX-1 and LX-2: new tools for analysis of hepatic fibrosis
    Xu, L
    Hui, AY
    Albanis, E
    Arthur, MJ
    O'Byrne, SM
    Blaner, WS
    Mukherjee, P
    Friedman, SL
    Eng, FJ
    [J]. GUT, 2005, 54 (01) : 142 - 151
  • [30] The tumor suppressor Smad4 DPC 4 as a central mediator of Smad function
    Zhang, Y
    Musci, T
    Derynck, R
    [J]. CURRENT BIOLOGY, 1997, 7 (04) : 270 - 276