IL‐17 and IL‐22 mediate IL‐20 subfamily cytokine production in cultured keratinocytes via increased IL‐22 receptor expression

• Published in: European journal of immunology 2009-10, Vol.39 (10), p.2779-2788
• Main Authors: Tohyama, Mikiko, Hanakawa, Yasushi, Shirakata, Yuji, Dai, Xjuju, Yang, Lujun, Hirakawa, Satoshi, Tokumaru, Sho, Okazaki, Hidenori, Sayama, Koji, Hashimoto, Koji
• Format: Article
• Language: English
• Subjects: beta-Defensins - genetics; Cells, Cultured; Chemokine; Chemokine CCL20 - genetics; Cytokine; Dermatitis; Epidermis - metabolism; Epithelial cells; Gene Expression - drug effects; Gene Expression - genetics; Heparin-binding EGF-like Growth Factor; Humans; Inflammation; Intercellular Signaling Peptides and Proteins - genetics; Interferon-gamma - pharmacology; Interleukin-10 Receptor beta Subunit - genetics; Interleukin-17 - pharmacology; Interleukin-1alpha - pharmacology; Interleukin-22; Interleukin-8 - genetics; Interleukins - genetics; Interleukins - metabolism; Interleukins - pharmacology; Keratinocytes - drug effects; Keratinocytes - metabolism; Models, Biological; Phosphorylation - drug effects; Psoriasis - metabolism; Receptors, Interleukin - genetics; Receptors, Interleukin - metabolism; STAT3 Transcription Factor - metabolism; Transduction, Genetic; Transforming Growth Factor alpha - genetics; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200939473

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‐3α, 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‐3α, 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.