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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.
AuthorsMikiko Tohyama, Yasushi Hanakawa, Yuji Shirakata, Xjuju Dai, Lujun Yang, Satoshi Hirakawa, Sho Tokumaru, Hidenori Okazaki, Koji Sayama, Koji Hashimoto
JournalEuropean journal of immunology (Eur J Immunol) Vol. 39 Issue 10 Pg. 2779-88 (Oct 2009) ISSN: 1521-4141 [Electronic] Germany
PMID19731362 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • CCL20 protein, human
  • Chemokine CCL20
  • DEFB4A protein, human
  • HBEGF protein, human
  • Heparin-binding EGF-like Growth Factor
  • IL19 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-10 Receptor beta Subunit
  • Interleukin-17
  • Interleukin-1alpha
  • Interleukin-8
  • Interleukins
  • Receptors, Interleukin
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Transforming Growth Factor alpha
  • Tumor Necrosis Factor-alpha
  • beta-Defensins
  • interleukin 20
  • interleukin-20 receptor
  • interleukin-22
  • interleukin-22 receptor
  • interleukin-24
  • Interferon-gamma
Topics
  • Cells, Cultured
  • Chemokine CCL20 (genetics)
  • Epidermis (metabolism)
  • Gene Expression (drug effects, genetics)
  • Heparin-binding EGF-like Growth Factor
  • Humans
  • Intercellular Signaling Peptides and Proteins (genetics)
  • Interferon-gamma (pharmacology)
  • Interleukin-10 Receptor beta Subunit (genetics)
  • Interleukin-17 (pharmacology)
  • Interleukin-1alpha (pharmacology)
  • Interleukin-8 (genetics)
  • Interleukins (genetics, metabolism, pharmacology)
  • Keratinocytes (drug effects, metabolism)
  • Models, Biological
  • Phosphorylation (drug effects)
  • Psoriasis (metabolism)
  • Receptors, Interleukin (genetics, metabolism)
  • STAT3 Transcription Factor (metabolism)
  • Transduction, Genetic
  • Transforming Growth Factor alpha (genetics)
  • Tumor Necrosis Factor-alpha (pharmacology)
  • beta-Defensins (genetics)

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