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首页> 外文期刊>The Journal of Biochemistry >Blockage by SP600125 of Fcepsilon receptor-induced degranulation and cytokine gene expression in mast cells is mediated through inhibition of phosphatidylinositol 3-kinase signalling pathway.
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Blockage by SP600125 of Fcepsilon receptor-induced degranulation and cytokine gene expression in mast cells is mediated through inhibition of phosphatidylinositol 3-kinase signalling pathway.

机译:SP600125对Fcepsilon受体诱导的脱颗粒和肥大细胞中细胞因子基因表达的阻断作用是通过抑制磷脂酰肌醇3激酶信号通路来介导的。

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摘要

SP600125 is used as a specific inhibitor of c-Jun N-terminal kinase (JNK). We initially aimed to examine physiological roles of JNK in mast cells that play a central role in inflammatory and immediate allergic responses. We found that Fc receptor for IgE (FcepsilonRI)-induced degranulation (serotonin release) and cytokine gene expression [interleukin (IL)-6, tumour necrosis factor-alpha and IL-13] in bone marrow-derived mast cells, were almost completely inhibited by SP600125. However, the time course of FcepsilonRI-induced JNK activation did not correlate with that of serotonin release. Furthermore, FcepsilonRI-induced degranulation and cytokine gene expression were not impaired in a JNK activator, MKK7-deficient mast cells, in which JNK activation was lost. These results indicate that the inhibitory effects by SP600125 are not due to impaired JNK activation. Instead, we found that SP600125 markedly inhibited the FcepsilonRI-induced activation of phosphatidylinositol 3-kinase (PI3K) and Akt, the same as a PI3K inhibitor, wortmannin. Finally, we found that SP600125 specifically inhibits delta form of p110 catalytic subunit (p110delta) of PI3K. Thus, SP600125 exerts its influence on mast cell functions by inhibiting the kinase activity of PI3K, but not JNK.
机译:SP600125用作c-Jun N末端激酶(JNK)的特异性抑制剂。我们最初旨在检查JNK在肥大细胞中的生理作用,肥大细胞在炎症和即时变态反应中起关键作用。我们发现在骨髓肥大细胞中,IgE(FcepsilonRI)诱导的脱粒(血清素释放)和细胞因子基因表达[白介素(IL)-6,肿瘤坏死因子-α和IL-13]的Fc受体几乎完全消失受SP600125抑制。但是,FcepsilonRI诱导的JNK激活的时间进程与血清素释放的时间进程无关。此外,FcepsilonRI诱导的脱粒和细胞因子基因表达在JNK激活剂MKK7缺陷的肥大细胞中丢失,而JNK激活丢失。这些结果表明,SP600125的抑制作用并非归因于JNK活化受损。相反,我们发现SP600125显着抑制FcepsilonRI诱导的磷脂酰肌醇3-激酶(PI3K)和Akt(与PI3K抑制剂渥曼青霉素相同)的活化。最后,我们发现SP600125特异抑制PI3K的p110催化亚基(p110delta)的三角形式。因此,SP600125通过抑制PI3K而不是JNK的激酶活性而对肥大细胞功能产生影响。

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