Interleukin (IL)-1 receptor-associated kinase (IRAK) requirement for optimal induction of multiple IL-1 signaling pathways and IL-6 production
Interleukin (IL)-1 receptor-associated kinase (IRAK) requirement for optimal induction of multiple IL-1 signaling pathways and IL-6 production
复制标题
DOI：
10.1084/jem.187.12.2073
复制
发表时间：
1998-06-15
影响因子：
15.3
通讯作者：
Fung-Leung, WP
中科院分区：
文献类型：
--
作者：
Kanakaraj, P;Schafer, PH;Fung-Leung, WP
白细胞介素(IL)-1是一种促炎细胞因子，在炎症中具有多效性。IL-1与其受体结合可触发一系列信号事件，包括激活应激激活的丝裂原活化蛋白（MAP）激酶、c-Jun nh2末端激酶（JNK）和p38 MAP激酶，以及转录因子核因子κ B （nf - κ B）。IL-1信号通过诱导炎症基因产物如IL-6导致细胞反应。IL-1信号传导最早的事件之一是IL-1受体相关激酶IRAK和IRAK-2与受体复合物的快速相互作用。IRAK和IRAK-2在IL-1信号通路和随后的细胞反应中的相对作用此前尚未确定。为了评估IRAK在IL-1信号传导中的重要性，制备并研究了IRAK缺陷小鼠成纤维细胞。在这里，我们报道il -1介导的JNK、p38和NF-kappa B的激活在缺乏IRAK表达的胚胎成纤维细胞中都降低了。此外，在irak缺乏的胚胎成纤维细胞和由irak缺乏的小鼠制备的皮肤成纤维细胞中，IL-6的产生响应IL-1也显著减少。我们的研究结果表明，IRAK在协调多种il -1信号通路以最佳诱导细胞反应中起着重要的近端作用。
Interleukin (IL)-1 is a proinflammatory cytokine with pleiotropic effects in inflammation. IL-1 binding to its receptor triggers a cascade of signaling events, including activation of the stress-activated mitogen-activated protein (MAP) kinases, c-Jun NH2-terminal kinase (JNK) and p38 MAP kinase, as well as transcription factor nuclear factor kappa B (NF-kappa B). IL-1 signaling results in cellular responses through induction of inflammatory gene products such as IL-6. One of the earliest events in IL-1 signaling is the rapid interaction of IL-1 receptor-associated kinases, IRAK and IRAK-2, with the receptor complex. The relative roles of IRAK and IRAK-2 in IL-1 signaling pathways and subsequent cellular responses have not been previously determined. To evaluate the importance of IRAK in IL-1 signaling, IRAK-deficient mouse fibroblast cells were prepared and studied. Here we report that IL-1-mediated activation of JNK, p38, and NF-kappa B were all reduced in embryonic fibroblasts deficient in IRAK expression. In addition, IL-6 production in response to IL-1 was also dramatically reduced in IRAK-deficient embryonic fibroblasts and in skin fibroblasts prepared from IRAK-deficient mice. Our results demonstrate that IRAK plays an essential proximal role in coordinating multiple IL-1signaling pathways for optimal induction of cellular responses.