诱导大鼠产生急性期反应会刺激其肝脏中α1（I）前胶原信使核糖核酸的表达。白细胞介素-6的可能作用。

Induction of an acute phase response in rats stimulates the expression of alpha 1(I) procollagen messenger ribonucleic acid in their livers. Possible role of interleukin-6.

作者信息

Greenwel P, Iraburu M J, Reyes-Romero M, Meraz-Cruz N, Casado E, Solis-Herruzo J A, Rojkind M

机构信息

Department of Medicine, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York.

出版信息

Lab Invest. 1995 Jan;72(1):83-91.

PMID:7837795

Abstract

BACKGROUND

In response to nonspecific inflammatory stimuli, circulating monocytes produce several cytokines that regulate the expression of liver acute phase protein genes. Patients with alcoholic liver disease have several manifestations of the acute phase response, including elevated serum levels of interleukin (IL)-1 (IL-1), IL-6 and tumor necrosis factor-alpha (TNF-alpha). However, the role of the acute phase response on liver fibrogenesis has not been explored.

EXPERIMENTAL DESIGN

In this communication we report experiments performed to investigate whether turpentine, an acute phase response inducer in rats has any effect on alpha 1 (I) procollagen gene expression in the liver. We also investigated which of the cytokines is responsible for the turpentine effect and whether IL-6 and TNF-alpha had an effect on alpha 1 (I) procollagen mRNA expression by liver fat-storing cells (FSC).

RESULTS

We show that alpha 1 (I) procollagen mRNA is increased in livers of turpentine-treated rats, and that an antibody to IL-6 as well as colchicine inhibit this effect. We also show that rIL-6 induces the expression of alpha 1 (I) procollagen mRNA in cultured FSC but not in hepatocytes. We demonstrated that the IL-6 effect is a transcriptional event that requires "de novo" protein synthesis. In addition to its effect on collagen gene expression, rIL-6 also stimulates expression of transforming growth factor-beta and fibronectin mRNAs. TNF-alpha inhibits alpha 1 (I) procollagen expression in FSC by 24 to 48 hours. However, TNF-alpha induces a transient expression of alpha 1 (I) procollagen mRNA by 2 to 3 hours. This increase is preceded by the induction of IL-6 mRNA.

CONCLUSIONS

We conclude that IL-6 produced during the acute phase response, alone or in conjunction with other cytokines, could play an important role in liver fibrogenesis by inducing the expression of collagen, fibronectin, and transforming growth factor-beta mRNAs in FSC.

摘要

背景

作为对非特异性炎症刺激的反应，循环中的单核细胞会产生多种细胞因子，这些细胞因子可调节肝脏急性期蛋白基因的表达。酒精性肝病患者具有急性期反应的多种表现，包括血清白细胞介素（IL）-1、IL-6和肿瘤坏死因子-α（TNF-α）水平升高。然而，急性期反应在肝脏纤维化形成中的作用尚未得到探讨。

实验设计

在本报告中，我们阐述了为研究大鼠急性期反应诱导剂松节油是否对肝脏α1（I）前胶原基因表达有影响而进行的实验。我们还研究了哪种细胞因子介导了松节油的作用，以及IL-6和TNF-α是否对肝脏贮脂细胞（FSC）的α1（I）前胶原mRNA表达有影响。

结果

我们发现，松节油处理的大鼠肝脏中α1（I）前胶原mRNA增加，而抗IL-6抗体以及秋水仙碱可抑制这种作用。我们还发现，重组IL-6可诱导培养的FSC中α1（I）前胶原mRNA的表达，但对肝细胞无此作用。我们证明，IL-6的作用是一个需要“从头”进行蛋白质合成的转录事件。除了对胶原基因表达的影响外，重组IL-6还刺激转化生长因子-β和纤连蛋白mRNA的表达。TNF-α在24至48小时内抑制FSC中α1（I）前胶原的表达。然而，TNF-α在2至3小时内诱导α1（I）前胶原mRNA的短暂表达。这种增加之前会诱导IL-6 mRNA的表达。