Project description:Atopic dermatitis (AD) is the most common chronic inflammatory skin disorder, characterized by intense itch and recurrent eczematous lesions. Due to lack of proper therapy, the strategies of T cell modulators in combination with targeting keratinocytes and/or myeloid cells might hold promise for achieving disease control in AD patients better than T cell modulators alone. we used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during HY209 treatment in mouse skin
Project description:Inflammation and autoimmunity are known as central processes in many skin diseases, including psoriasis. It is therefore important to develop pre-clinical models that describe disease-related aspects to enable testing of pharmaceutical drug candidates and formulations to essentially develop safe and effective treatments. A widely accepted pre-clinical model of psoriasis is the imiquimod (IMQ)-induced skin inflammation mouse model. It is primarily used to assess safety and efficacy of drug candidates for treatment of psoriasis but can also be used to evaluate the performance of drug delivery systems. In this model, topically applied IMQ provokes local skin inflammation, which is characterized by elevated levels of cytokines and chemokines, cellular infiltration, and increased epidermal thickness. In this study, we investigated the abundance of a subset of matrix metalloproteinases (MMPs) in skin from mice with IMQ-induced skin inflammation and skin from naïve mice using targeted proteomics. Our findings revealed a significant increase in the abundance of MMP-2, MMP-7, MMP-8, and MMP-13 after treatment with IMQ compared to the control skin, while MMP-3, MMP-9, and MMP-10 were exclusively detected in the IMQ-treated skin. The increased abundance and broader representation of MMPs in the IMQ-treated skin provide valuable insight into the pathophysiology of skin inflammation in the IMQ model. Specifically, the changes in the MMP profiles observed in the IMQ-treated skin resemble the MMP patterns found in skin lesions of individuals with psoriasis. Ultimately, the differences in MMP abundance under IMQ-induced inflammation as compared to non-inflamed control skin can be exploited as a model to investigate drug efficacy or performance of drug delivery systems.
Project description:To assess the preclinical Aldara model, the proteomic response of mouse skin to topical applied Aldara cream was assessed using untargeted LC-MS. Skin from sham treated or treated with the Aldara cream were compared for 4 independent experiments after 8 days of treatment.
Project description:We identified zinc-alpha-2-glycoprotein (ZAG), a 41-kDa adipokine that regulates body weight, lipid, and mobilization, as a novel biomarker for AD. ZAG levels were consistently decreased in sera, T cells, and skin in human AD patients compared with healthy controls. We used microarrays to obtain the change of signaling molecules by topical treatment of recombinant ZAG using atopic dermatitis induced mouse model.
Project description:Winged bean (WB), Psophocarpus tetragonolobus, is a tropical legume, the potential of which is not yet been understood. We found that a 5 week-oral administration of WB seed extract inhibited wrinkle formation induced by repeated tape stripping (TS), which is a model of lichenification in human chronic eczematous dermatitis. To elucidate mechanism of the effect of WB on this model, we applied microarray analysis. Skin barrier was disrupted by repeated application and removal (tape stripping; TS) of cellophane tape on the dorsal skin of the left side. This procedure was started after 1 week-administration of winged bean (WB) extract, and was conducted 3 times per week for 4 weeks. Dorsal skin samples from three experimental groups were used for microarray experiment. These groups were the non-TS (NT), TS, and TS with oral administration of WB extract (TS/WB). The DNA microarray experiment was performed using Affymetrix Mouse Genome 430 2.0 Array.