Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an inhibitor of autoimmune inflammation and cell cycle progression

被引:306
作者
Song, KM
Chen, YG
Göke, R
Wilmen, A
Seidel, C
Göke, A
Hilliard, B
Chen, YH
机构
[1] Univ Penn, Sch Med, Inst Human Gene Therapy, Philadelphia, PA 19104 USA
[2] Univ Penn, Sch Med, Dept Mol & Cellular Engn, Philadelphia, PA 19104 USA
关键词
autoimmunity; inflammation; apoptosis; cytokine; TRAIL;
D O I
10.1084/jem.191.7.1095
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis of tumor cells but not normal cells; its role in normal nontransformed tissues is unknown. We report here that chronic blockade of TRAIL in mice exacerbated autoimmune arthritis, and that intraarticular TRAIL gene transfer ameliorated the disease. In vivo, TRAIL blockade led to profound hyperproliferation of synovial cells and arthritogenic lymphocytes and heightened the production of cytokines and autoantibodies. In vitro, TRAIL inhibited DNA synthesis and prevented cell cycle progression of lymphocytes. Interestingly, TRAIL had Ilo effect on apoptosis of inflammatory cells either in vivo or in vitro. Thus, unlike other members of the tumor necrosis factor superfamily, TRAIL is a prototype inhibitor protein that inhibits autoimmune inflammation by blocking cell cycle progression.
引用
收藏
页码:1095 / 1103
页数:9
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