title: IL-17 and IL-22 mediate IL-20 subfamily cytokine production in cultured keratinocytes via increased IL-22 receptor expression.
abstract: IL-20 cytokine subfamily members, including IL-19, IL-20, and IL-24, are highly expressed in psoriatic skin lesions. Here, we demonstrate that psoriasis mediators IL-17 and IL-22 synergistically induce the production of IL-20 subfamily proteins in cultured human keratinocytes. Interestingly, expression of the IL-22 receptor (IL-22R) also increased in epidermal lesions versus normal skin. IL-22R over-expression using an adenoviral vector to mimic psoriatic conditions in cultured keratinocytes significantly enhanced IL-17- and IL-22-induced production of IL-20 subfamily cytokines. Furthermore, IL-17 and IL-22 coordinately enhanced MIP-3alpha, IL-8, and heparin-binding EGF-like growth factor (HB-EGF) production, depending on the amount of IL-22R expression. Additionally, because IL-20 and IL-24 share the IL-22R with IL-22, the function of IL-20 and IL-24 was also increased. IL-20 and IL-24 have effects similar to that of IL-22; IL-24 showed more potent expression than IL-20. A combination of IL-24 and IL-17 increased the production of MIP-3alpha, IL-8, and HB-EGF, as did a combination of IL-22 and IL-17. These data indicate that increased IL-22R expression in epidermal keratinocytes contributes to the pathogenesis of psoriasis through enhancing the coordinated effects of IL-22 and IL-17, inducing the production of the IL-20 subfamily, chemokines, and growth factors.
authors.affiliation: Department of Dermatology, Ehime University Graduate School of Medicine, Shitsukawa, Toon-city, Ehime 791-0295, Japan. tohm@m.ehime-u.ac.jp
authors.forename: Mikiko
authors.initials: M
authors.lastname: Tohyama
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hanakawa
authors.forename: Yuji
authors.initials: Y
authors.lastname: Shirakata
authors.forename: Xjuju
authors.initials: X
authors.lastname: Dai
authors.forename: Lujun
authors.initials: L
authors.lastname: Yang
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirakawa
authors.forename: Sho
authors.initials: S
authors.lastname: Tokumaru
authors.forename: Hidenori
authors.initials: H
authors.lastname: Okazaki
authors.forename: Koji
authors.initials: K
authors.lastname: Sayama
authors.forename: Koji
authors.initials: K
authors.lastname: Hashimoto
mesh_terms: D002478:Cells, Cultured; D054418:Chemokine CCL20 / Q000235:genetics; D004817:Epidermis / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D007371:Interferon-gamma / Q000494:pharmacology; D053710:Interleukin-10 Receptor beta Subunit / Q000235:genetics; D020381:Interleukin-17 / Q000494:pharmacology*; D053582:Interleukin-1alpha / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics; D007378:Interleukins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D010766:Phosphorylation / Q000187:drug effects; D011565:Psoriasis / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014161:Transduction, Genetic; D016211:Transforming Growth Factor alpha / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D023083:beta-Defensins / Q000235:genetics; D000097043:Interleukin-22; D000099180:Interleukin-24
chemical_list: D054418:Chemokine CCL20; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma; D053710:Interleukin-10 Receptor beta Subunit; D020381:Interleukin-17; D053582:Interleukin-1alpha; D016209:Interleukin-8; D007378:Interleukins; D018123:Receptors, Interleukin; D050796:STAT3 Transcription Factor; D016211:Transforming Growth Factor alpha; D014409:Tumor Necrosis Factor-alpha; D023083:beta-Defensins; D000097043:Interleukin-22; D000099180:Interleukin-24; C108355:CCL20 protein, human; C106641:DEFB4A protein, human; C587883:HBEGF protein, human; C421250:IL19 protein, human; C494086:STAT3 protein, human; C492510:interleukin-20 receptor; C415369:interleukin-22 receptor; C422042:interleukin 20