IL-4 regulation of p38 MAPK signalling is dependent on cell type
IL-4 regulation of p38 MAPK signalling is dependent on cell type
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DOI：
10.1006/cyto.2002.1043
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发表时间：
2002-06-21
期刊：
影响因子：
3.8
通讯作者：
Foxwell, BMJ
中科院分区：
文献类型：
--
作者：
Hunt, AE;Williams, LM;Foxwell, BMJ
p38 MAPK最初与JNK沿着被表征为应激诱导的激酶。随后，发现p38 MAPK被细胞应激以外的刺激物激活，如生长因子和有丝分裂原，如白细胞介素（IL）-2，IL-7和IL-3。一个值得注意的例外是IL-4，因为肥大细胞中的研究显示这种细胞因子没有激活p38 MAPK。在这项研究中，我们表明，p38 MAPK的调节是细胞类型依赖性的。与通过γ（gamma）（c）传递信号的其他细胞因子一样，IL-4可以激活CT6 T细胞系和BA/F3前B细胞中的p38 MAPK。然而，IL-4不能激活鼠巨噬细胞系RAW 264.7中的p38 MAPK，并且确实，细胞长期暴露于IL-4导致LPS诱导的MAPK激活的抑制。该结果与IL-4对肿瘤坏死因子α（TNF α）产生的明确的抑制作用相关。相反，在原代人单核细胞中的研究表明，长时间暴露于IL-4导致LPS刺激的p38 MAPK活化增强;这与TNF α产生增强相关。这些数据突出了IL-4信号传导机制的复杂性，通过给定的细胞因子调节给定信号传导途径中可能存在的多样性，此外，还表明了不同细胞系统之间的外推可能产生的问题。(C)2002爱思唯尔科技有限公司版权所有。
p38 MAPK was originally characterized as a stress-induced kinase, along with JNK. Subsequently, p38 MAPK was found to be activated by stimuli other than cellular stress, such as growth factors and mitogens, like interleukin (IL)-2, IL-7 and IL-3. A notable exception was IL-4, as studies in mast cells showed no activation of p38 MAPK by this cytokine. In this study we show that the regulation of p38 MAPK is cell type dependent. Like other cytokines that signal through the gamma (gamma)(c), IL-4 can activate p38 MAPK in the CT6 T-cell line and BA/F3 pro-B-cells. However, IL-4 was unable to activate p38 MAPK in the murine macrophage cell line, RAW 264.7 and, indeed, prolonged exposure of cells to IL-4 results in suppression of LPS-induced MAPK activation. This result correlates with the well defined inhibitory effect of IL-4 on tumour necrosis factor alpha (TNFalpha) production. In contrast, studies in primary human monocytes showed that prolonged exposure to IL-4 resulted in enhanced activation of LPS-stimulated p38 MAPK; this correlated with an enhanced TNFalpha production. These data highlight the complexity of IL-4 signalling mechanisms, the diversity that can exist in the regulation of a given signalling pathway by a given cytokine and, furthermore, indicate the problems that can arise from extrapolation between different cell systems. (C) 2002 Elsevier Science Ltd. All rights reserved.