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:Female C57BL/6J mice, 8 weeks old, were DNCB-induced dermatitis on skin. For the effect of tonsil-derived mesenchymal stem cells (T-MSCs)treatment, cells were added to dermatitis model. After 10 days, spleen cells were isolated for RNA expression analysis.
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.