Leukocyte-derived koebnerisin (S100A15) and psoriasin (S100A7) are systemic mediators of inflammation in psoriasis

Background: Psoriasis is a systemic immune-mediated chronic inflammatory disease. In the skin, the antimicrobial proteins koebnerisin (S100A15) and psoriasin (S100A7) are overexpressed in the epidermis of psoriatic lesions and mediate inflammation as chemoattractants for immune cells. Their role for systemic inflammation in circulating leukocytes is unknown. Objective: The aim of the study was to identify circulating leukocyte populations as a source of koebnerisin and psoriasin. Further, immune-stimulatory effects of these S100A proteins on circulating leukocytes were evaluated and their role as therapeutic response markers in patients with psoriasis was analyzed upon UVB treatment. Methods: The expression and production of koebnerisin and psoriasin by leukocytes were assessed by quantitative real-time PCR (qRT-PCR) and immunoblotting.The S100A protein mediated regulation of proinflammatory cytokines by peripheral blood mononuclear cells (PBMCs) was measured with qRT-PCR and cytometric bead assay. Results: We identified circulating leukocytes as novel sources of koebnerisin (S100A15) and psoriasin (S100A7). Circulating leukocytes (PBMCs) of patients with psoriasis produced increased levels of koebnerisin and psoriasin compared to healthy individuals. Both S100A proteins further acted as 'alarmins' on PBMC to induce proinflammatory cytokines implicated in the pathogenesis of psoriasis, such as IL-1 beta TNF-alpha, IL-6 and IL-8. Koebnerisin levels were suppressed in PBMC of psoriatic patients when effectively treated with narrow-band UVB. Conclusions: Data suggest that koebnerisin and psoriasin are systemic pro-inflammatory mediators and koebnerisin acts as a therapeutic response marker in psoriasis. (C) 2015 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.