Aleksandra Batycka-Baran1, Eva Hattinger2, Stephanie Zwicker2, Burkhard Summer2, O M Zack Howard3, Peter Thomas2, Jacek C Szepietowski4, Thomas Ruzicka2, Jörg C Prinz2, Ronald Wolf5. 1. Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wroclaw, Poland; Department of Dermatology and Allergology, Ludwig-Maximilian University, Munich, Germany. 2. Department of Dermatology and Allergology, Ludwig-Maximilian University, Munich, Germany. 3. Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, MD, USA. 4. Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wroclaw, Poland. 5. Department of Dermatology and Allergology, Ludwig-Maximilian University, Munich, Germany. Electronic address: ronald.wolf@med.uni-muenchen.de.
Abstract
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-1β, TNF-α, 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.
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-1β, TNF-α, IL-6 and IL-8. Koebnerisin levels were suppressed in PBMC of psoriaticpatients 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.