Inhibition of CD40 signaling pathway by tyrphostin A1 reduces secretion of IL-12 in macrophage, Th1 cell development and experimental allergic encephalomyelitis in SJL/J mice
Inhibition of CD40 signaling pathway by tyrphostin A1 reduces secretion of IL-12 in macrophage, Th1 cell development and experimental allergic encephalomyelitis in SJL/J mice
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DOI：
10.1016/s0165-5728(00)00434-3
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发表时间：
2001-03-01
影响因子：
3.3
通讯作者：
Sriram, S
中科院分区：
文献类型：
--
作者：
Du, C;Bright, JJ;Sriram, S
CD40与其配体相互作用激活抗原提呈细胞是IL-12产生和Th1分化的关键共刺激信号。酪氨酸蛋白是一种有机分子，可以抑制蛋白酪氨酸激酶的磷酸化。我们发现Tyrphostin Al抑制CD40L刺激的巨噬细胞培养中IL-12的产生和抗原诱导的Th1细胞的产生。我们的数据还表明，Tyrphostin Al阻断了CD40L诱导的NF-KB向细胞核的移位，并降低了IL-12p40基因的激活。AZ的体内治疗导致髓鞘碱性蛋白(MBP)特异性脑源性T细胞的生成减少。此外，用铝治疗SJL/J小鼠可减轻实验性变态反应性脑脊髓炎(EAE)。(C)2001 Elsevier Science B.V.保留所有权利。
Activation of antigen presenting cells through the interaction of CD40 with its ligand is a critical co-stimulatory signal for IL-12 production and Th1 differentiation. Tyrphostins are organic molecules that inhibit the phosphorylation of protein tyrosine kinases. We show that tyrphostin Al inhibits CD40L-stimulated IL-12 production in macrophage cultures and antigen-induced generation of Th1 cells. Our data also show that tyrphostin Al blocks CD40L-induced translocation of NF-KB to the nucleus, and reduces the activation of IL-12 p40 gene. In vivo therapy with AZ leads to decrease in generation of myelin basic protein (MBP) specific encephalitogenic T cells. In addition, treatment of SJL/J mice with Al results in attenuation of experimental allergic encephalomyelitis (EAE). (C) 2001 Elsevier Science B.V. All rights reserved.