REGULATION OF T-CELL ACTIVATION BY CYTOCHROME-P450 INHIBITORS

被引:16
作者
AUSSEL, C [1 ]
BREITTMAYER, JP [1 ]
TICCHIONI, M [1 ]
PELASSY, C [1 ]
BERNARD, A [1 ]
机构
[1] HOP ARCHET,CENT IMMUNOL LAB,F-06202 NICE 03,FRANCE
关键词
D O I
10.1006/cimm.1994.1136
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Cytochrome P450 inhibitors such as a-naphthoflavone, the imidazole antimycotics, econazole, clotrimazole, and miconazole and the lipoxygenase inhibitors, nordihydroguaiaretic acid and eicosatetraynoic acid, strongly diminished CD3-induced human T cell proliferation. This effect is due to a marked inhibition of IL-2 synthesis. The mechanism leading to the in vitro immunosuppressive effect of cytochrome P450 inhibitors appears to be a consequence of a blockade of Ca2+ influx induced by CD3 mAb. The drugs tested did not interfere with the release of Ca2+ from the endoplasmic reticulum as demonstrated by Ca2+ measurements in the presence of the Ca2+ chelator, EGTA. Measurements of CD3-induced changes in phosphatidylserine synthesis, which reflect the status (full/empty) of intracellular Ca2+ stores confirmed that CD3 mAb remained able to empty the Ca2+ stores either alone or in the presence of cytochrome P450 inhibitors. Altogether, our results support the hypothesis that a cytochrome P450 regulates Ca2+ influx in T cells and are consistent with the proposal that impairing Ca2+ influx leads to the inhibition of IL-2 synthesis and subsequent T cell proliferation. (C) 1994 Academic Press, Inc.
引用
收藏
页码:436 / 445
页数:10
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