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: Mikiko Tohyama, Yasushi Hanakawa, Yuji Shirakata, Xjuju Dai, Lujun Yang, Satoshi Hirakawa, Sho Tokumaru, Hidenori Okazaki, Koji Sayama, Koji Hashimoto
• Journal: European journal of immunology (Eur J Immunol) Vol. 39 Issue 10 Pg. 2779-88 (Oct 2009) ISSN: 1521-4141 [Electronic] Germany
• PMID: 19731362 (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 receptor
• interleukin-22 receptor
• interleukin-24
• Interferon-gamma
• interleukin 20
• interleukin-22

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)