The role of IL-33 and its reseptor in contact hypersensitivity reaction

我们研究了野生型和可溶性ST2转基因小鼠对FITC和恶唑酮的超敏反应。这些小鼠的耳厚度和组织病理学观察没有统计学差异。UVB、IFNG和IL-17诱导培养的正常人表皮角质形成细胞(NHEKs)表达IL-33。NHEK对IL-33表达的诱导依赖于EGFR和ERK。在IL-17和IFNG的情况下，诱导也依赖于STAT1和JAK。我们在外显子2的上游发现了三个不同的外显子1。将IL-33可能的启动子区域克隆到荧光素酶载体中，并在第二外显子1的5‘侧翼区(外显子1b)确定了活性启动子区域。该启动子区域在NHEKs、正常人真皮成纤维细胞和人脐静脉内皮细胞中具有活性。启动子活性在IFNG和IL-17的刺激下被诱导，这与我们的蛋白质和信使核糖核酸结果一致。

We investigated the hypersensitivity reaction to FITC and oxazolone in wild type and soluble ST2 transgenic mice. There were no statistical differences in ear thickness and histopathological observasion in these mice. UVB, IFNg, and IL-17 induced IL-33 expression in protein and mRNA levels in cultured normal human epidermal keratinocytes (NHEKs). The induction of IL-33 expression in NHEKs was dependent on EGFR and ERK with these stimulations. In case of IL-17 and IFNg, the induction was dependent also on STAT1 and JAK. We have identified three distinct exon1s in the upstream of exon2. The putative promoter regions of IL-33 were cloned into luciferase vectors, and we identified active promoter region in the 5'flanking region of second exon1 (exon1b). This promoter region was active in NHEKs, normal human dermal fibroblasts, and human umbilical vein endothelial cells. The promoter activity was induced by the stimulation with IFNg and IL-17, consistent to our protein and mRNA results.