Analysis of oxidative stress induction in fibroblasts and fibroblast and keratinocyte crosstalk in a 2-dimensional Atopic Dermatitis model

Evidence spreads that oxidative stress plays a role in the pathophysiology of Atopic Dermatitis (AD). As there is not much known about oxidative stress and the role of fibroblasts in AD, in vitro models of AD have been established and examined. AD-model fibroblasts exhibit elevated basal levels of intracellular oxidative stress compared to a control. Stress induction leads to even higher levels of reactive oxygen species (ROS) and AD-model fibroblasts react more sensitive to this treatment than control fibroblasts. By inhibiting nicotinamide adenine dinucleotide phosphate (NADPH)-oxidases the level of oxidative stress is reduced, therefore it can be assumed that fibroblasts produce ROS in response to oxidative stress which leads to a positive feedback cycle of ROS generation. The cell viability is not reduced in AD-model fibroblasts compared to a control, while it is reduced by the induction of oxidative stress. The induction of oxidative stress leads to DNA damage which can be abrogated by inhibiting NADPH oxidases. There is no difference in the extent of damage between AD-model and control fibroblasts. The ability of fibroblasts to cope with oxidative stress seems to be unaffected by AD. The induction of oxidative stress leads to an activation of both pro-apoptotic and pro-survival pathways and promotes inflammation. Crosstalk experiments showed that fibroblasts induce a stronger reaction towards oxidative stress in keratinocytes. Keratinocytes induce a stronger reaction towards oxidative stress in fibroblasts but in a more powerful way. In both cases the reaction could be suppressed by inhibiting NADPH oxidases, therefore it can be assumed that the reaction is mediated by NADPH oxidases. It can be assumed that both keratinocytes and fibroblasts secrete factors that prime the other cells to react more sensitive to subsequent oxidative stress and lead to a reinforcement of oxidative stress in neighbouring tissues.


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