INTERFERON-ALFA AND INTERFERON-GAMMA INHIBIT PROLIFERATION AND COLLAGEN-SYNTHESIS OF HUMAN ITO CELLS IN CULTURE
INTERFERON-ALFA AND INTERFERON-GAMMA INHIBIT PROLIFERATION AND COLLAGEN-SYNTHESIS OF HUMAN ITO CELLS IN CULTURE
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DOI：
10.1002/hep.1840210418
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发表时间：
1995-04-01
期刊：
影响因子：
13.5
通讯作者：
MAVIER, P
中科院分区：
文献类型：
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作者：
MALLAT, A;PREAUX, AM;MAVIER, P
在持续的肝纤维化过程中，Ito细胞获得成肌纤维细胞的特征，增殖，并合成增加量的细胞外基质成分。干扰素（IFN）α和IFN γ已显示在间充质来源的各种细胞培养物中引起抗增殖和/或抗纤维化作用。本研究的目的是研究IFN-α和IFN-γ对培养的人肌成纤维细胞Ito细胞（MFBIC）增殖和胶原合成与分泌的影响。血清刺激的掺入[H-3]胸腺嘧啶核苷到DNA的MFBIC的剂量依赖性减少两种细胞因子。IFN-α（10（4）U/mL）和IFN-γ（10（3）U/mL）分别使DNA合成减少69%和66%。通过细胞计数证实细胞增殖的抑制。当用血小板衍生生长因子（PDGF-BB、PDGF-AA）或转化生长因子（TGF）-β 1刺激细胞生长时，观察到类似的结果。每细胞的胶原蛋白分泌抑制两种细胞因子，评估[H-3]羟脯氨酸掺入。在6天处理后，IFN-γ在抑制新合成的胶原蛋白分泌方面显示出比IFN-α更大的效力（在10（2）U/mL IFN-γ和10（4）U/mL IFN-α存在下，分别为对照的41%和48%）。IFN-α和IFN-γ同时降低静止期MFBIC中I型和III型前胶原信使RNA（mRNA）的稳态表达。活力测定排除了两种分子的细胞毒性作用。最后，无论是通过免疫印迹法还是北方印迹分析，两种IFN均降低平滑肌α-肌动蛋白（SM α-肌动蛋白）的表达。我们得出结论，IFN-α和IFN-γ抑制增殖以及胶原蛋白的合成在人MFBIC。
During the course of ongoing liver fibrogenesis, Ito cells acquire myofibroblastic features, proliferate, and synthesize increased amounts of extracellular matrix components. Interferon (IFN) alfa and IFN gamma have been shown to elicit antiproliferative and/or antifibrogenic effects in various cell cultures of mesenchymal origin. The aim of this study was to investigate the effects of IFN-alpha and IFN-gamma on cultured human myofibroblastic Ito cells (MFBIC) proliferation and collagen synthesis and secretion. Serum-stimulated incorporation of [H-3]thymidine into DNA of MFBIC was dose-dependently decreased by both cytokines. IFN-alpha (10(4) U/mL) and IFN-gamma (10(3) U/mL) decreased DNA synthesis by 69% and 66%, respectively. Inhibition of cell proliferation was confirmed by cell counting. Similar results were observed when cell growth was stimulated with platelet-derived growth factor (PDGF-BB, PDGF-AA) or transforming growth factor (TGF)-beta 1. Collagen secretion per cell was inhibited by both cytokines, as assessed by [H-3]hydroxyproline incorporation. After a 6-day treatment, IFN-gamma showed a greater potency than IFN-alpha in inhibiting secretion of newly synthetized collagen (41% and 48% of control in the presence of 10(2) U/mL of IFN-gamma and 10(4) U/mL of IFN-alpha, respectively). Both IFN-alpha and IFN-gamma concurrently decreased steady-state expression of type I and type III procollagen messenger RNAs (mRNAs) in quiescent MFBIC. Viability assays ruled out cytotoxic effects of the two molecules. Finally, both IFNs decreased smooth muscle alpha-actin (SM alpha-actin) expression, whether assayed by immunobloting or by Northern blot analysis. We conclude that IFN-alpha and IFN-gamma inhibit proliferation as well as collagen synthesis in human MFBIC.