A novel role for IL-15 in the regulation of redox state in stressed mouse skin (P5086)

Abstract The association of IL-15 with a range of inflammatory disorders has implicated its function in innate immune response. Several isoforms of IL-15 mRNA generated by alternative splicing have been found constitutively expressed in normal mouse tissues at low level. An ENU mutagenized mouse (pedigree 191) bears a mutation in the exon 7 of IL-15 mRNA. Although the transcriptional level of the canonical IL-15 mRNA in P191 was comparable with B6 wild type skin, a transcript generated from alternatively spliced exon 7 of IL-15 mRNA (IL-15_ASE7) was increased by 8 folds in the epidermis of mutant mice. Mechanical stimulation induced downregulation of IL-15 mRNA in B6 but less reduced in P191 abraded skin which also exhibited attenuated dermal cellular infiltration and reduced expression of IL-1β, TNF-α and IL-6 transcripts. Moreover, genome-wide transcriptional profiling of B6 and P191 abraded skin by DNA microarray analysis showed that genes involved in oxidative phosphorylation and glutathione metabolism were distinguishably expressed between B6 and P191 abraded skin. Particularly, transcriptional levels of Uqcrb gene encoding components of the mitochondrial respiratory chain complex III and anti-oxidant Sod-1 gene were significantly reduced in P191 skin at 48 hours after abrasion. Detailed mechanisms by which IL-15 controls the redox state in epidermal keratinocytes as well as the regulatory role of IL-15_ASE7 on IL-15 action will be elucidated.