INTERLEUKIN 6 ROLE IN ALCOHOLIC LIVER CIRRHOSIS
白细胞介素 6 在酒精性肝硬化中的作用
基本信息
- 批准号:2389919
- 负责人:
- 金额:$ 18.91万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1995
- 资助国家:美国
- 起止时间:1995-04-01 至 2000-03-31
- 项目状态:已结题
- 来源:
- 关键词:acute phase protein adipocytes alcoholic liver cirrhosis antifibrinolytic agents antiinflammatory agents colchicine collagen collagenase cytokine cytokine receptors disease /disorder model extracellular matrix fibrogenesis fibrosis gene expression inflammation interleukin 1 interleukin 6 laboratory rat liver cells liver pharmacology northern blottings tissue /cell culture tissue inhibitor of metalloproteinases tumor necrosis factor alpha
项目摘要
Liver cirrhosis is among the leading causes of death worldwide.
Approximately 50% of the deaths attributable to liver cirrhosis recognize
alcohol as the main ethiologic agent. Currently, there is no accepted
treatment for this disease. The available treatment is directed primarily
to complications of cirrhosis and not to inhibit the inflammatory or
fibrogenic mechanisms. Close to 3 billion dollars were spent for the
treatment of patients with liver cirrhosis in 1992. Therefore, the
development of a treatment for this disease will relieve the suffering of
hundreds of thousands and will save the USA government millions of
dollars. Patients with alcoholic hepatitis have several of the
manifestations of the acute-phase response (APR). They also have elevated
levels of IL-1, IL-6 and TNF-alpha. These same cytokines are involved in
cell injury and production of extracellular matrix by liver fat-storing
cells. We have obtained evidence to suggest that IL-6 is a fibrogenic
cytokine that induces the expression of alpha1(I) procollagen mRNA. In
addition, TNF-alpha is a cytokine that mediates cell injury. Therefore,
drugs that inhibit synthesis and/or secretion of cytokines or that prevent
their biological activity could ameliorate liver cirrhosis. Colchicine is
an orphan drug that has been used successfully for the treatment of
cirrhosis. However, its mechanism of action remains to be elucidated.
Recent evidence suggests that colchicine inhibits the release of cytokines
and growth factors, prevents the cytotoxic effect of TNF-alpha and
enhances the release of TNF-alpha soluble receptors. The long-term
objectives of this proposal are to evaluate the contribution of the APR,
and of IL-1, IL-6 and TNF-alpha in the development of liver cirrhosis and
explore the anti-inflammatory and anti-fibrogenic potential of colchicine.
Our specific aims are: (1) To investigate the mechanisms by which the APR
contributes to liver fibrosis and to determine the molecular mechanisms by
which cytokines modulate type I collagen gene expression in fat-storing
cells. The mechanisms by which colchicine prevents the APR will be
explored. (2) To study the role of IL-1, IL-6 and TNF-alpha in inducing
excess matrix deposition in a rat model of alcoholic cirrhosis, and
evaluate the effectiveness of colchicine as a therapeutic agent for
alcoholic liver cirrhosis. If we could better understand the mechanisms
by which colchicine prevents liver fibrosis and improves liver function we
could test the anti-inflammatory and anti-fibrogenic potential of many
compounds, including a large number of colchicine derivatives currently
available.
肝硬化是全世界最主要的死亡原因之一。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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MARCOS ROJKIND其他文献
MARCOS ROJKIND的其他文献
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{{ truncateString('MARCOS ROJKIND', 18)}}的其他基金
INTERLEUKIN 6 ROLE IN ALCOHOLIC LIVER CIRRHOSIS
白细胞介素 6 在酒精性肝硬化中的作用
- 批准号:
6371374 - 财政年份:1995
- 资助金额:
$ 18.91万 - 项目类别:
INTERLEUKIN 6 ROLE IN ALCOHOLIC LIVER CIRRHOSIS
白细胞介素 6 在酒精性肝硬化中的作用
- 批准号:
6128654 - 财政年份:1995
- 资助金额:
$ 18.91万 - 项目类别:
INTERLEUKIN 6 ROLE IN ALCOHOLIC LIVER CIRRHOSIS
白细胞介素 6 在酒精性肝硬化中的作用
- 批准号:
6629598 - 财政年份:1995
- 资助金额:
$ 18.91万 - 项目类别:
INTERLEUKIN 6 ROLE IN ALCOHOLIC LIVER CIRRHOSIS
白细胞介素 6 在酒精性肝硬化中的作用
- 批准号:
6495544 - 财政年份:1995
- 资助金额:
$ 18.91万 - 项目类别:
INTERLEUKIN 6 ROLE IN ALCOHOLIC LIVER CIRRHOSIS
白细胞介素 6 在酒精性肝硬化中的作用
- 批准号:
6731971 - 财政年份:1995
- 资助金额:
$ 18.91万 - 项目类别:
INTERLEUKIN 6 ROLE IN ALCOHOLIC LIVER CIRRHOSIS
白细胞介素 6 在酒精性肝硬化中的作用
- 批准号:
6509228 - 财政年份:1995
- 资助金额:
$ 18.91万 - 项目类别:
INTERLEUKIN 6 ROLE IN ALCOHOLIC LIVER CIRRHOSIS
白细胞介素 6 在酒精性肝硬化中的作用
- 批准号:
2047189 - 财政年份:1995
- 资助金额:
$ 18.91万 - 项目类别:
INTERLEUKIN 6 ROLE IN ALCOHOLIC LIVER CIRRHOSIS
白细胞介素 6 在酒精性肝硬化中的作用
- 批准号:
7052752 - 财政年份:1995
- 资助金额:
$ 18.91万 - 项目类别:
Role of Acetaldehyde on PDGF-BB-induced HSC Migration
乙醛对 PDGF-BB 诱导的 HSC 迁移的作用
- 批准号:
7050518 - 财政年份:1995
- 资助金额:
$ 18.91万 - 项目类别:
Role of Acetaldehyde on PDGF-BB-induced HSC Migration and Proliferation.
乙醛对 PDGF-BB 诱导的 HSC 迁移和增殖的作用。
- 批准号:
7228134 - 财政年份:1995
- 资助金额:
$ 18.91万 - 项目类别:
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