069 Reactive oxygen species produced by myeloid cells in psoriasis as a potential biofactor contributing to the development of vascular inflammation

Psoriasis is an immune-mediated inflammatory skin disease mainly driven by interleukin 17A (IL-17A) and associated with cardiovascular dysfunction. Here we used a severe psoriasis mouse model of dermal IL-17A overexpression (K14-IL-17Aind/+, IL-17Aind/+ control mice) to investigate the activity neutrophils potential cellular interconnection between vasculature. Levels reactive oxygen species (ROS) its release were measured lucigenin- or luminol-based assays, respectively. Neutrophilic inflammation-related markers in aorta determined RT-PCR. For tracking skin-derived immune cells PhAM-K14-IL-17Aind/+ mice allowing us mark all photoconversion fluorescent protein analyzing their migration into spleen, lymph nodes flow cytometry. In comparison controls, K14-IL-17Aind/+ revealed elevated ROS levels higher neutrophilic oxidative burst accompanied upregulation several activation markers. line these results psoriatic displayed expression CXCL2 S100A9, genes involved neutrophil migration. Yet, found no direct cell from aortic vessel wall. Although showed activated phenotype, did not find connection manifestations, suggesting that highly active vasculature-invading are originating directly bone-marrow. Hence, skin-vasculature crosstalk most likely based on systemic effects, emphasizing importance holistic therapeutic approach for patients suffering psoriasis. revision BioFactors