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

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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.