Feedback inhibition of macrophage tumor necrosis factor-α production by tristetraprolin

被引：998

作者：

Carballo, E

Lai, WS

Blackshear, PJ ^{[1
]}

机构：

[1] NIEHS, Off Clin Res, Res Triangle Pk, NC 27709 USA

[2] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA

[3] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA

[4] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA

来源：

SCIENCE | 1998年 / 281卷 / 5379期

关键词：

D O I：

10.1126/science.281.5379.1001

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Tumor necrosis factor-alpha (TNF-alpha) is a major mediator of both acute and chronic inflammatory responses in many diseases. Tristetraprolin (TTP), the prototype of a class of Cys-Cys-Cys-His (CCCH) zinc finger proteins, inhibited TNF-alpha production from macrophages by destabilizing its messenger RNA. This effect appeared to result from direct TTP binding to the AU-rich element of the TNF-alpha messenger RNA. TTP is a cytosolic protein in these cells, and its biosynthesis was induced by the same agents that stimulate TNF-alpha production. including TNF-alpha itself. These findings identify TTP as a component of a negative feedback Loop that interferes with TNF-alpha production by destabilizing its messenger RNA. This pathway represents a potential target for anti-TNF-alpha therapies.

引用

页码：1001 / 1005

页数：5

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