Interleukin 17 Drives Vascular Inflammation, Endothelial Dysfunction, and Arterial Hypertension in Psoriasis-Like Skin Disease

• DOI: 10.1161/atvbaha.114.304108
• Publication Date: 2014-10-24T03:34:32Z
• Authors: Susanne Karbach; Andrew L. Croxford; Matthias Oelze; Rebecca Schüler; Daniel Minwegen; Joanna Wegner; Lija Koukes; Nir Yogev; Alexei Nikolaev; Sonja Reißig; Alexander Ullmann; Maike Knorr; Maximilian Waldner; Markus F. Neurath; Huige Li; Zhixiong Wu; Christoph Brochha...; Jürgen Scheller; Stefan Rose-John; Carolin Piotrowski; Ingo Bechmann; Markus Radsak; Philipp Wild; Andreas Daiber; Esther von Stebut; Philip Wenzel; Ari Waisman; Thomas Münzel
• Keywords: Endothelial Dysfunction

Interleukin (IL)-17A is regarded as an important cytokine to drive psoriasis, inflammatory skin disease marked by increased cardiovascular mortality. We aimed test the hypothesis that overproduction of IL-17A in leading dermal inflammation may systemically cause vascular dysfunction psoriasis-like disease.Conditional overexpression keratinocytes caused severe mice (K14-IL-17A(ind/+) mice), associated with reactive oxygen species formation and circulating CD11b(+) leukocytes blood, endothelial dysfunction, systolic blood pressure, left ventricular hypertrophy, reduced survival compared controls. In K14-IL-17A(ind/+) mice, immunohistochemistry flow cytometry revealed production nitric oxide/superoxide reaction product peroxynitrite infiltration vasculature myeloperoxidase(+)CD11b(+)GR1(+)F4/80(-) cells accompanied expression inducible oxide synthase nicotinamide dinucleotide phosphate (NADPH) oxidase, nox2. Neutrophil depletion anti-GR-1 antibody injections oxidative stress vessels. Neutralization tumor necrosis factor-α IL-6 (both downstream IL-17A) lesions, attenuated heart partially improved mice.Dermal induces systemic stress, arterial hypertension, increases mortality mainly driven cells. Depletion GR-1(+) immune or neutralization cytokines biologicals attenuates phenotype mice.