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首页> 外文期刊>Cytokine >Inhibitors of Src-family tyrosine kinases favour Th2 differentiation.
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Inhibitors of Src-family tyrosine kinases favour Th2 differentiation.

机译：Src家族酪氨酸激酶的抑制剂有利于Th2分化。

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摘要

Two potent pyrazolo-pyrimidine inhibitors of Src-family kinases were found to enhance interleukin 4 (IL-4) and reduce interferon gamma(IFN-gamma) production in cultures of splenocytes from ovalbumin-specific TCR-transgenic BALB/c mice. The effect was increased by addition of a monoclonal antibody binding to domains 3/4 of CD4, while other antibodies binding to domain 1 had the opposite effect. The inhibitors suppressed CD40 ligand (CD40L) expression on activated CD4 T cells, which may explain this Th2 differentiating effect. More generally, the effect fits within the overall framework of signal attenuation in T cells driving this form of differentiation. The inhibitors did not revert previously induced Th1 differentiation in serial cultures of the TCR-transgenic cells. Drugs with this activity are of obvious interest as probes and potential therapeutic agents in autoimmune disease. Copyright 1999 Academic Press.
机译：在卵清蛋白特异性TCR转基因BALB / c小鼠脾细胞培养物中，发现两种Src家族激酶的有效吡唑并嘧啶抑制剂可增强白介素4（IL-4）并降低干扰素γ（IFN-γ）的产生。通过添加与CD4的结构域3/4结合的单克隆抗体，可以增加效果，而与结构域1结合的其他抗体则具有相反的效果。抑制剂抑制了活化的CD4 T细胞上的CD40配体（CD40L）表达，这可以解释这种Th2分化作用。更一般而言，该效应适合于驱动这种分化形式的T细胞中信号衰减的总体框架。该抑制剂在TCR转基因细胞的连续培养中没有还原先前诱导的Th1分化。具有这种活性的药物作为自身免疫性疾病的探针和潜在治疗剂，具有明显的兴趣。版权所有1999，学术出版社。

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