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银屑病T细胞中的酪氨酸磷酸化受到诱导或改善银屑病的药物的调节。

Tyrosine phosphorylation in psoriatic T cells is modulated by drugs that induce or improve psoriasis.

作者信息

Ockenfels H M, Nussbaum G, Schultewolter T, Mertins K, Wagner S N, Goos M

机构信息

Department of Dermatology, University of Essen, Germany.

出版信息

Dermatology. 1995;191(3):217-25. doi: 10.1159/000246549.

Abstract

BACKGROUND

The induction of protein tyrosine kinases (PTKs) is known to be a key element in the activation of lymphocytes.

OBJECTIVE

Because immunologic mechanisms are important in the pathogenesis of psoriasis, we examined the time course of tyrosine-phosphorylated proteins (p-tyr) as a marker for cellular PTK activity in phytohemagglutinin (PHA)-stimulated T cells of psoriatic patients and healthy controls.

METHODS AND RESULTS

PHA-stimulated T cells from both groups expressed peaks of p-tyr after 15 min and 4 h. In T cells from psoriatics, the 15-min peak was smaller but the 4-hour peak reached an enormous maximum, which was 270% higher than the basic p-tyr value. PHA-stimulated T cells were additionally treated with psoriasis-provoking drugs (lithium, chloroquine, propranolol and ethanol) and the two immunosuppressive drugs cyclosporin A and FK 506. Lithium and propranolol were able to increase the p-tyr level after 15 min in PHA-stimulated T cells from psoriatics in contrast to controls. Chloroquine and ethanol did not have a significant effect on T cells of both groups. CsA markedly diminished the phosphorylation of intracellular tyrosines in T cells of psoriatics and controls, whereas FK 506 diminished the p-tyr level in controls only slightly.

CONCLUSION

We have characterized important differences in p-tyr phosphorylation activities of psoriatic T cells compared to controls. This could be a hint to explain the known abnormalities of psoriatic T cells.

摘要

背景

已知蛋白酪氨酸激酶(PTK)的诱导是淋巴细胞激活的关键因素。

目的

由于免疫机制在银屑病发病机制中很重要,我们检测了酪氨酸磷酸化蛋白(p-tyr)的时间进程,作为银屑病患者和健康对照者经植物血凝素(PHA)刺激的T细胞中细胞PTK活性的标志物。

方法与结果

两组经PHA刺激的T细胞在15分钟和4小时后均出现p-tyr峰值。在银屑病患者的T细胞中,15分钟时的峰值较小,但4小时时的峰值达到极大值,比基础p-tyr值高270%。经PHA刺激的T细胞还分别用诱发银屑病的药物(锂、氯喹、普萘洛尔和乙醇)以及两种免疫抑制药物环孢素A和FK 506进行处理。与对照组相比,锂和普萘洛尔能够增加银屑病患者经PHA刺激的T细胞在15分钟后的p-tyr水平。氯喹和乙醇对两组T细胞均无显著影响。环孢素A显著降低了银屑病患者和对照组T细胞内酪氨酸的磷酸化水平,而FK 506仅轻微降低了对照组的p-tyr水平。

结论

我们已明确银屑病患者T细胞与对照组相比在p-tyr磷酸化活性方面存在重要差异。这可能是解释银屑病患者T细胞已知异常情况的一个线索。

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