title: Vitamin D analog calcipotriol suppresses the Th17 cytokine-induced proinflammatory S100 "alarmins" psoriasin (S100A7) and koebnerisin (S100A15) in psoriasis.
abstract: The antimicrobial peptides (AMP) psoriasin (S100A7) and koebnerisin (S100A15) are differently induced in psoriatic skin. They act synergistically as chemoattractants and "alarmins" to amplify inflammation in psoriasis. Th17 cytokines are key players in psoriasis pathogenesis and vitamin D analogs feature anti-psoriatic effects; both of these activities could be mediated through epidermal AMP regulation. We show that supernatants of cultured psoriatic T cells induce and release psoriasin and koebnerisin from keratinocytes and the Th17 cytokines IL-17A, tumor necrosis factor-α, and IL-22 differently regulate psoriasin and koebnerisin reflecting their distinct expression pattern in normal and psoriatic skin. IL-17A is the principal inducer of both S100 and their expression is further amplified by cooperating Th17 cytokines in the micromilieu of psoriatic skin. Increased extracellular psoriasin and koebnerisin also synergize as "alarmins" to prime epidermal keratinocytes for production of immunotropic cytokines that further amplify the inflammatory response. Treatment of psoriatic plaques with the vitamin D analog calcipotriol interferes with the S100-mediated positive feedback loop by suppressing the increased production of psoriasin and koebnerisin in psoriatic skin and their Th17-mediated regulation in epidermal keratinocytes. Thus, targeting the S100-amplification loop could be a beneficial anti-inflammatory approach in psoriasis and other inflammatory skin diseases.
authors.affiliation: Department of Dermatology and Allergology, Ludwig-Maximilian University, Munich, Germany.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Hegyi
authors.forename: Stephanie
authors.initials: S
authors.lastname: Zwicker
authors.forename: Daniela
authors.initials: D
authors.lastname: Bureik
authors.forename: Mark
authors.initials: M
authors.lastname: Peric
authors.forename: Sarah
authors.initials: S
authors.lastname: Koglin
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Batycka-Baran
authors.forename: Jörg C
authors.initials: JC
authors.lastname: Prinz
authors.forename: Thomas
authors.initials: T
authors.lastname: Ruzicka
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schauber
authors.forename: Ronald
authors.initials: R
authors.lastname: Wolf
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D003879:Dermatologic Agents / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism; D011565:Psoriasis / Q000276:immunology* / Q000378:metabolism; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000187:drug effects / Q000378:metabolism*; D058504:Th17 Cells / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D023181:Antimicrobial Cationic Peptides; D002117:Calcitriol; D003879:Dermatologic Agents; D020381:Interleukin-17; D007378:Interleukins; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; D014409:Tumor Necrosis Factor-alpha; D000097043:Interleukin-22; C089242:S100A7 protein, human; C510475:S100A7A protein, human; C055085:calcipotriene