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

In the autoimmune skin disease psoriasis, an overproduction of interleukin-17A and interleukin-23 leads to an aberrant activation of keratinocytes, influx of myeloid cells and skin inflammation. These inflammatory conditions led to a higher activation of neutrophil granulocytes in a mouse model of chronic severe psoriasis based on IL-17A overexpression in the skin (K14-IL-17Aind/+ mice versus IL-17Aind/+ controls) seen by upregulated production of reactive oxygen species (ROS) and significant increase of mRNA expression ofmyeloperoxidase (Mpo),proteinase 3 (Prt3), andneutrophil elastase (Elane). In skin of psoriatic mice, increased ROS-levels were detected and we had previously also found increased ROS levels in the aortic vessel wall. In both skin and aorta, significantly increased mRNA-expression levels ofChemokine (C-X-C motif)ligand 2 (Cxcl2) andS100 calcium-binding protein A9 (S100a9) were detected. No direct migration of myeloid cells from the inflamed skin into the vasculature was found in K14-IL-17Aind/+ psoriatic mice, so ROS producing myeloid cells were most likely bone marrow derived underlining the systemic effects of the disease. AbstractPsoriasis is an immune-mediated inflammatory skin disease driven by interleukin-17A (IL-17A) and associated with cardiovascular dysfunction. We used a severe psoriasis mouse model of keratinocyte IL-17A overexpression (K14-IL-17Aind/+, IL-17Aind/+ control mice) to investigate the activity of neutrophils and a potential cellular i...
Source: BioFactors - Category: Biochemistry Authors: Tags: RESEARCH ARTICLE Source Type: research