Regulation of human airway epithelial cell IL-8 expression by MAP kinases
Regulation of human airway epithelial cell IL-8 expression by MAP kinases
复制标题
DOI：
10.1152/ajplung.00060.2002
复制
发表时间：
2002-10-01
影响因子：
4.9
通讯作者：
Hershenson, MB
中科院分区：
文献类型：
--
作者：
Li, J;Kartha, S;Hershenson, MB
最近的研究表明，IL-8蛋白的最大表达需要NF-kappaB的激活以及MAP激酶ERK、JNK和p38的激活。然而，NF-kappaB反式活化与MAP激酶活化之间的确切关系尚不清楚。我们在人支气管上皮细胞系中检测了tnf - α诱导的IL-8启动子转录对NF-kappaB、ERK、JNK和p38的要求。tnf α诱导所有三种MAP激酶的激活。使用化学和显性阴性抑制剂的组合，我们发现抑制NF-kappaB， ERK和JNK，但不抑制p38，每个都减少了tnf - α诱导的IL-8启动子转录。JNK信号的抑制也显著降低了tnf - α诱导的NF-kappaB的转激活，而ERK和p38的抑制则没有效果。另一方面，ERK对于tnf α诱导的激活因子蛋白(AP)-1启动子序列的激活是必需的和充分的，这些启动子序列共同起着基础水平增强子的作用。AP-1的活化也需要JNK活化。最后，抑制p38降低了IL-8蛋白的丰度，表明p38以转录后方式调节IL-8的表达。我们得出结论，在人气道上皮细胞中，MAP激酶可能通过nf - kappab依赖性（在JNK的情况下）和非依赖性（ERK）过程以及转录后机制调节IL-8启动子活性（p38）。
Recent studies indicate that maximal IL-8 protein expression requires activation of NF-kappaB as well as activation of the MAP kinases ERK, JNK, and p38. However, the precise relationship between NF-kappaB transactivation and MAP kinase activation remains unclear. We examined the requirements of NF-kappaB, ERK, JNK, and p38 for TNF-alpha-induced transcription from the IL-8 promoter in a human bronchial epithelial cell line. Treatment with TNF-alpha-induced activation of all three MAP kinases. Using a combination of chemical and dominant-negative inhibitors, we found that inhibition of NF-kappaB, ERK, and JNK, but not p38, each decreased TNF-alpha-induced transcription from the IL-8 promoter. Inhibition of JNK signaling also substantially reduced TNF-alpha-induced NF-kappaB transactivation, whereas inhibition of ERK and p38 had no effect. On the other hand, ERK was required and sufficient for TNF-alpha-induced activation of activator protein (AP)-1 promoter sequences, which together function as a basal level enhancer. JNK activation was also required for AP-1 transactivation. Finally, inhibition of p38 attenuated IL-8 protein abundance, suggesting that p38 regulates IL-8 expression in a posttranscriptional manner. We conclude that, in human airway epithelial cells, MAP kinases may regulate IL-8 promoter activity by NF-kappaB-dependent (in the case of JNK) and -independent (ERK) processes, as well as by posttranscriptional mechanisms (p38).