Cytokine regulation of hepatic stellate cells in liver fibrosis
Cytokine regulation of hepatic stellate cells in liver fibrosis
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DOI：
10.1111/j.1530-0277.1999.tb04202.x
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发表时间：
1999-05-01
影响因子：
3.2
通讯作者：
Tsukamoto, H
中科院分区：
文献类型：
--
作者：
Tsukamoto, H
细胞因子是肝星状细胞(HSCs)在体外和体内“激活”的主要介质。它们主要分为促有丝分裂因子(转化生长因子-α、血小板衍生生长因子、白介素1、肿瘤坏死因子-α和胰岛素样生长因子)和致纤维化细胞因子(转化生长因子-β和白介素6)。除了它们的有丝分裂(刺激细胞增殖)和纤维化(诱导基质蛋白)特性外，它们在体外还被证明具有独特的细胞变化，这些变化被认为是HSC“激活”的关键特征，包括失去维生素A，刺激迁移，增强细胞收缩能力，以及诱导基质金属蛋白酶和金属蛋白酶组织抑制物。细胞因子的潜在细胞来源包括肝巨噬细胞、内皮细胞、胆管上皮细胞、淋巴细胞、血小板、肝细胞和活化的HSCs。为了更好地了解细胞因子/趋化因子在HSC“激活”中的作用方式和致病意义，需要解决以下四个问题：(1)HSC还表达哪些细胞因子来建立关键的自分泌刺激？(2)HSC刺激的内源性或外源性启动因子是什么？(3)转化生长因子-β是关键的纤维化细胞因子，其激活机制是什么？(4)HSC衍生的促炎介质在肝纤维化中有多重要？这篇综述将讨论这些问题，以及目前对细胞因子在HSC激活中的作用的理解。
Cytokines constitute a major class of mediators responsible for "activation" of hepatic stellate cells (HSCs) in vitro and in vivo. They are largely divided into mitogenic (transforming growth factor-alpha, platelet-derived growth factor, interleukin-1, tumor necrosis factor-alpha, and insulin-like growth factor) and fibrogenic (transforming growth factor-beta and interleukin-6) cytokines. In addition to their mitogenic (stimulation of cell proliferation) and fibrogenic (induction of matrix proteins) properties, they are also shown to confer in vitro unique cellular changes known to be the key features of HSC "activation," including loss of vitamin A, stimulation of migration, enhanced cellular contractility, and matrix metalloproteinase and tissue inhibitor of metalloproteinase induction. Potential cellular sources of the cytokines consist of hepatic macrophages, endothelial cells, biliary epithelial cells, lymphocytes, platelets, hepatocytes, and activated HSCs. To better understand the mode of actions and the pathogenetic significance of cytokines/chemokines involved in "activation" of HSCs, the following four questions need to be addressed: (1) What other cytokines are expressed by HSCs to establish critical autocrine stimulation? (2) What are endogenous or exogenous priming factors for HSC stimulation? (3) What is the mechanism of activation for transforming growth factor-beta, the pivotal fibrogenic cytokine? (4) How important are HSC-derived proinflammatory mediators in liver fibrosis? This review will discuss these questions, along with the current understanding of the role of cytokines in HSC activation.