inflammation. For control number 1, blister fluid was obtained from a bedridden elderly male person that developed a mechanical blister in the inguinal region in the course of mobilization procedures during patient care. The person is considered healthy in the sense of non-EB and without any bullous or other 
skin diseases. For control number 2, mechanical blisters were induced deliberately on both heels by a healthy volunteer from our lab by wearing unfitting shoes. Finally, considering control number 3, a blister developed on the foot of a healthy person after a burn accident. No traces of blood and no signs of inflammation, pruritus or unusual pain occurred with the blisters of the three healthy controls. Taken together, by comparison of EBS blister fluids with the control samples described above, we consider the obtained in vivo data to be valid. Kallikrein Expression in EBS-DM Cell Lines The increased expression of KLK5 and KLK7 in the two EBSDM cell lines KEB-7 and EBDM-1 indicated a potential role in the pathophysiology of Dowling-Meara-related blister formation. Hypothetically, kallikreins could play a role in acantholysis, the separation of cell-cell contacts, but there are only few reports of Dowling-Meara patients that show signs of acantholysis. Nevertheless, since we did not observe any differences in KLK5 and KLK7 expression in patients blister fluids vs. controls, their role as potential therapeutic targets can not be suggested. As the expression of kallikreins as well as of junction proteins could be a sign of keratinocyte terminal differentiation, we analysed the microarray data for differentiation-related genes, such as involucrin, filaggrin, loricrin, small proline-rich proteins and SPINK5/LEKTI. Out of 14 investigated genes, 6 were upregulated in KEB7 but none were upregulated in EBDM-1. We analysed these genes with SQRT-PCR and found IVL and FLG increased in KEB-7 and SPINK5/LEKTI in EBDM-1. Western blot confirmed the increase 7528253 of IVL in KEB-7. FLG could not be detected on the protein level, and SPINK5/LEKTI showed no differences between patient cell lines vs. NEB-1, or between EBS patients blister fluids vs. controls. The fact, that differentiation-related proteins were expressed in only one cell line, but most of the targets were expressed in both cell lines, does not support the idea of a pure cell culture artefact due to keratinocyte differentiation. Molecular Pathomechanisms in Dowling-Meara: IL-1b, MMP-9 and CXCL8/IL-8 In the study of Wally et al., IL-1b was shown to be the inaugurating mediator of the Dowling-Meara phenotype observed in the EBS-DM cell lines KEB-7 and EBDM-1. The same study showed activation of the JNK stress pathway through IL-1b, and amelioration of the phenotype in vitro by depleting IL-1b with a neutralizing antibody. Based on that knowledge, the present study investigated the gene and protein expression profiles of KEB-7 and EBDM-1 and showed that expression of these genes is dependent on IL-1b signaling. Of course, the question remains, how does IL-1b mediate these effects and how are the molecular mechanisms IMR 1 interconnected Fig. 8 shows an overview of the pathways described below. In the case of the Cdc42 pathway, inflammatory cytokines such as TNFa and IL-1 were shown to influence actin cytoskeleton dynamics by 11408530 activation of Cdc42, and interconnections between IL-1 and Cdc42 signaling are known . Cdc42 activates downstream targets like the ERM proteins, and phosphoezrin recruits the GEF