title: Leukocyte-derived koebnerisin (S100A15) and psoriasin (S100A7) are systemic mediators of inflammation in psoriasis.
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.
authors.affiliation: Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wroclaw, Poland; Department of Dermatology and Allergology, Ludwig-Maximilian University, Munich, Germany.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Batycka-Baran
authors.affiliation: Department of Dermatology and Allergology, Ludwig-Maximilian University, Munich, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Hattinger
authors.affiliation: Department of Dermatology and Allergology, Ludwig-Maximilian University, Munich, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Zwicker
authors.affiliation: Department of Dermatology and Allergology, Ludwig-Maximilian University, Munich, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Summer
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, MD, USA.
authors.forename: O M
authors.initials: OM
authors.lastname: Zack Howard
authors.affiliation: Department of Dermatology and Allergology, Ludwig-Maximilian University, Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Thomas
authors.affiliation: Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Jacek C
authors.initials: JC
authors.lastname: Szepietowski
authors.affiliation: Department of Dermatology and Allergology, Ludwig-Maximilian University, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ruzicka
authors.affiliation: Department of Dermatology and Allergology, Ludwig-Maximilian University, Munich, Germany.
authors.forename: Jörg C
authors.initials: JC
authors.lastname: Prinz
authors.affiliation: Department of Dermatology and Allergology, Ludwig-Maximilian University, Munich, Germany. Electronic address: ronald.wolf@med.uni-muenchen.de.
authors.forename: Ronald
authors.initials: R
authors.lastname: Wolf
mesh_terms: D000328:Adult; D000368:Aged; D016207:Cytokines / Q000097:blood* / Q000235:genetics; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D016209:Interleukin-8 / Q000097:blood / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000097:blood* / Q000235:genetics / Q000532:radiotherapy; D012313:RNA / Q000097:blood; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000097:blood* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics; D014467:Ultraviolet Therapy; D055815:Young Adult
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; C510475:S100A7A protein, human; D014409:Tumor Necrosis Factor-alpha; D012313:RNA
keywords: Koebnerisin; Leukocytes; Psoriasin; Psoriasis; S100; UVB