title: Epidermal overexpression of interleukin-19 and -20 mRNA in psoriatic skin disappears after short-term treatment with cyclosporine a or calcipotriol.
abstract: Interleukin-19, 20, and 24 are new members of the IL-10 family binding and signaling through the IL-20R1/IL-20R2 heterodimer, while IL-20 and 24 also bind to the IL-20R2/IL-22R1 heterodimer. Using in situ hybridization we have studied mRNA expression of IL-19, 20, and 24 and their related receptor chains in skin from psoriatic patients before and during short-term treatment with either oral cyclosporine A or topical calcipotriol. In untreated lesions IL-19 and IL-20 mRNA was expressed focally in epidermis above the dermal papillae, whereas IL-24 was expressed in mononuclear cells in the dermal infiltrate. The expression of IL-19 and 20 mRNA was confined to the basal and suprabasal keratinocytes. No expression of IL-19 and 20 mRNA could be detected in uninvolved psoriatic skin. Treatment with cyclosporine A and calcipotriol resulted in disappearance of the IL-19 and 20 mRNA. Expression of mRNA for the receptor chains IL-20R1 and IL-20R2 was found throughout the psoriatic epidermal layer, whereas IL-22R1 mRNA was predominantly expressed in the superficial part of the psoriatic epidermis. These findings show that IL-19 and IL-20 are synthesized by a distinct population of keratinocytes. It remains to be clarified whether IL-19 and IL-20 are implicated in the pathogenesis of psoriasis.
authors.affiliation: Discovery, Novo Nordisk, Bagsvaerd, Denmark.
authors.forename: John
authors.initials: J
authors.lastname: Rømer
authors.forename: Erik
authors.initials: E
authors.lastname: Hasselager
authors.forename: Peder Lisby
authors.initials: PL
authors.lastname: Nørby
authors.forename: Torben
authors.initials: T
authors.lastname: Steiniche
authors.forename: Jes
authors.initials: J
authors.lastname: Thorn Clausen
authors.forename: Knud
authors.initials: K
authors.lastname: Kragballe
mesh_terms: D002117:Calcitriol / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D016572:Cyclosporine / Q000008:administration & dosage*; D003879:Dermatologic Agents / Q000008:administration & dosage*; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D016147:Genes, Tumor Suppressor; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D007378:Interleukins / Q000235:genetics; D015603:Keratinocytes / Q000187:drug effects; D011565:Psoriasis / Q000188:drug therapy* / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D018123:Receptors, Interleukin / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects; D000099180:Interleukin-24
chemical_list: D002117:Calcitriol; D016572:Cyclosporine; D003879:Dermatologic Agents; D016753:Interleukin-10; D007378:Interleukins; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D000099180:Interleukin-24; C421250:IL19 protein, human; C415369:interleukin-22 receptor; C055085:calcipotriene; C422042:interleukin 20