The house dust mite allergen Der p 1, unlike Der p 3, stimulates the expression of interleukin-8 in human airway epithelial cells via a proteinase-activated receptor-2-independent mechanism
The house dust mite allergen Der p 1, unlike Der p 3, stimulates the expression of interleukin-8 in human airway epithelial cells via a proteinase-activated receptor-2-independent mechanism
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DOI：
10.1074/jbc.m507140200
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发表时间：
2006-03-17
影响因子：
4.8
通讯作者：
Jacquet, A
中科院分区：
文献类型：
--
作者：
Adam, E;Hansen, KK;Jacquet, A
我们研究并比较了两种尘螨蛋白水解过敏原 Der p 1 和 Der p 3 以及蛋白酶激活受体 2 (PAR(2)AP) 的肽激动剂触发人肺上皮细胞 (A549) 释放白细胞介素 (IL)-8 的机制。尽管测试的所有三种刺激均诱导 IL-8（mRNA 和蛋白质）上调，但 Der p 1 介导的信号转导事件与 PAR(2)AP 和 Der p 3 诱导的信号事件并不完全匹配。首先，Der p 1 在刺激 IL-8 基因转录活性方面不如 PAR(2)AP 和 Der p 3 有效。其次，Der p 1 介导的 IL-8 表达主要依赖于 NF-kappa B，而 Der p 3 和 PAR(2)AP 通过激活 NF-κ B 和 AP-1 调节 IL-8 表达。第三，虽然所有三种 MAP 激酶 ERK1/2、p38 和 JNK 均被激活，但 Der p 1 仅通过 ERK1/2 信号通路诱导 IL-8 释放，而 PAR(2)AP 和 Der p 3 也涉及其他激酶。第四，在 HeLa 细胞中，Der p 1 能够独立于 PAR(2) 表达上调 IL-8 分泌，并且与 PAR(2)AP 和 Der p 3 相比，Der p 1 无法通过表达 PAR(2) 的 KNRK 细胞中的 PAR(2) 影响钙信号传导。最后，Der p 1 对代表 PAR(2) N 端激活切割位点的合成肽的切割不会像 Der p 3 那样释放 PAR(2) 的高效激活剂。我们得出结论，Der p 1（但不是 Der p 3）诱导 A549 上皮细胞中 IL-8 的产生与 PAR(2) 激活无关。
We investigated and compared the mechanisms by which two dust mite proteolytic allergens, Der p 1 and Der p 3, and a peptide agonist of proteinase-activated receptor 2 (PAR(2)AP) trigger interleukin (IL)-8 release from human pulmonary epithelial cells (A549). Although all three stimuli tested induced the up-regulation of IL-8 ( mRNA and protein), the Der p 1-mediated signaling events did not exactly match those induced by PAR(2)AP and Der p 3. First, Der p 1 was less effective in stimulating IL-8 gene transcriptional activity than PAR(2)AP and Der p 3. Second, Der p 1-mediated IL-8 expression was mainly dependent on NF-kappa B, whereas Der p 3 and PAR(2)AP regulated IL-8 expression through the activation of both NF-kappa B and AP-1. Third, although all three MAP kinases, ERK1/2, p38, and JNK, were activated, Der p 1 induced IL-8 release exclusively via the ERK1/2 signaling pathway, whereas PAR(2)AP and Der p 3 also involved the other kinases. Fourth, in HeLa cells, Der p 1 was able to up-regulate IL-8 secretion independent of PAR(2) expression, and in contrast with PAR(2)AP and Der p 3, Der p 1 was unable to affect calcium signaling via PAR(2) in PAR(2)-expressing KNRK cells. Finally, cleavage by Der p 1 of a synthetic peptide representing the N-terminal activation-cleavage site of PAR(2) did not release a high potency activator of PAR(2) as does Der p 3. We conclude that Der p 1 ( but not Der p 3)-induced IL-8 production in A549 epithelial cells is independent of PAR(2) activation.