Melanoma-Directed Activation of Apoptosis Using a Bispecific Antibody Directed at MCSP and TRAIL Receptor-2/Death Receptor-5

lymphopoietin expression in parallel with a reduction in serine protease activity and elevation in b-glucocerebrosidase activity (Figures 1 and 2, and Supplementary Figures S1 and S2), suggesting not only that coapplication of PAR2 antagonist and LBA could be involved in both PAR2-independent and PAR2-dependent mechanisms, but also that it might be essential to account for both mechanisms to confer significant therapeutic benefits in AD. Meanwhile, the antipruritic effect from inhibiting PAR2 signaling also could be involved in the therapeutic effects, although we could not evaluate quantitatively the degree of itch in this study. This study demonstrates that coapplications of a PAR2 antagonist and the polyhydroxy acid LBA could represent a novel therapeutic strategy that simultaneously addresses the two mechanisms of AD pathogenesis, namely, skin barrier abnormality and allergic inflammation. The study results form the basis for further evaluation of this strategy in other AD animal models and in human AD. All experiments with mice were approved by the Ethics of Animal Experimentation Committee of Oita University.