Induction of inflammatory cytokines by a keratin mutation in a mouse model for EBS

Epidermolysis bullosa simplex (EBS) is a skin disorder caused by mutations in keratin (K) 5 or K14 genes. It is widely regarded as a mechanobullous disease, resulting from a weakened cytoskeleton, causing extensive cytolysis. It was postulated by others that certain K14 mutations induce TNF-alfa and increase apoptosis. Here, we report that in K5-/- mice , the mRNA and protein levels of TNF-alfa remain unaltered. Transcriptome analysis of K5-/- mice revealed however, that the pro-inflammatory cytokines interleukin-6 and interleukin-1beta were significantly upregulated at the mRNA level in K5-/- mouse skin. These results were confirmed by TaqMan real-time PCR and ELISA assays. We hypothesize that keratin mutations contribute to EBS in a mouse model by inducing local inflammation that mediates a stress response. Keywords: comparative gene expression profile Two groups were K5-/- skin and wildtype . Six animals were included in each group. All the total RNA samples were isolated from tissues taken immediately after birth, and were pooled for later microarray experiments. Using realtime PCR and ELISA analysis confirmed our microarray result.