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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cells, Cultured
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Chemokine CCL20 / genetics
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Epidermis / metabolism
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Gene Expression / drug effects
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Gene Expression / genetics
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Heparin-binding EGF-like Growth Factor
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Humans
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Intercellular Signaling Peptides and Proteins / genetics
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Interferon-gamma / pharmacology
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Interleukin-10 Receptor beta Subunit / genetics
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Interleukin-17 / pharmacology*
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Interleukin-1alpha / pharmacology
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Interleukin-22
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Interleukin-8 / genetics
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Interleukins / genetics
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Interleukins / metabolism*
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Interleukins / pharmacology*
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Keratinocytes / drug effects
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Keratinocytes / metabolism*
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Models, Biological
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Phosphorylation / drug effects
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Psoriasis / metabolism*
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Receptors, Interleukin / genetics
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Receptors, Interleukin / metabolism*
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STAT3 Transcription Factor / metabolism
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Transduction, Genetic
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Transforming Growth Factor alpha / genetics
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Tumor Necrosis Factor-alpha / pharmacology
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beta-Defensins / genetics
Substances
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CCL20 protein, human
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Chemokine CCL20
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DEFB4A protein, human
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HBEGF protein, human
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Heparin-binding EGF-like Growth Factor
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IL19 protein, human
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Intercellular Signaling Peptides and Proteins
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Interleukin-10 Receptor beta Subunit
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Interleukin-17
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Interleukin-1alpha
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Interleukin-8
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Interleukins
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Receptors, Interleukin
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STAT3 Transcription Factor
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STAT3 protein, human
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Transforming Growth Factor alpha
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Tumor Necrosis Factor-alpha
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beta-Defensins
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interleukin-20 receptor
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interleukin-22 receptor
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interleukin-24
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Interferon-gamma
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interleukin 20