INDUCTION OF TRANSCRIPTION FACTORS IN HUMAN T-LYMPHOCYTES BY ASPIRIN-LIKE DRUGS

被引:13
作者
FLESCHER, E
LEDBETTER, JA
OGAWA, N
VELAROCH, N
FOSSUM, D
DANG, H
TALAL, N
机构
[1] UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284
[2] BRISTOL MYERS SQUIBB PHARMACEUT RES INST,SEATTLE,WA 98121
关键词
D O I
10.1016/0008-8749(95)80033-F
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Aspirin-like drugs (ALD) induce calcium mobilization, an essential component of T cell activation, but do not induce the biosynthesis of IL-2. To understand the extent to which ALD may mimic mitogenic stimulation, we studied cytoplasmic and nuclear signaling steps in ALD-treated T cells. We found that ALD induce a transient activation of protein kinase (PKC) but have no effect (in comparison to anti-CD3 antibodies) on protein tyrosine phosphorylation nor on PCL gamma 1 tyrosine phosphorylation. ALD-induced calcium mobilization and PKC activation are independent of tyrosine protein kinase activity as shown by the lack of effect of herbimycin, a tyrosine-protein kinase-specific inhibitor. Although we detected no IL-2 mRNA in ALD-treated cells, the nuclei of these cells contain proteins capable of binding to three regulatory sequences in the IL-2 promoter region: NFAT, NF kappa B, and AP-1. These binding activities are expressed only in activated T cells. The expression of AP-1 depended on calcium mobilization and PKC activation. These data suggest that ALD cause transient but significant changes in T cell transmembrane signaling, although some events induced by stimulation with anti-CD3 antibodies are not induced by ALD. The signal is transmitted to the nucleus and induces DNA-binding activity by several transcription factors. However, the ALD stimulus is not capable of causing complete T cell activation. (C) 1995 Academic Press, Inc.
引用
收藏
页码:232 / 239
页数:8
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