IL-22 and IL-20 are key mediators of the epidermal alterations in psoriasis while IL-17 and IFN-gamma are not
| Autor: | Harald S. Haugen, Monica Anderson, Katarzyna Warszawska, Sandra Philipp, Kim Waggie, Ellen Witte, Wolfram Sterry, Katrin Witte, Wenfeng Xu, Hans-Dieter Volk, Elmar vom Baur, Kerstin Wolk, Robert Sabat, Caroline Johnson-Leger |
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| Rok vydání: | 2008 |
| Předmět: |
Keratinocytes
STAT3 Transcription Factor medicine.medical_treatment Blotting Western Enzyme-Linked Immunosorbent Assay Mice Inbred Strains Mice Transgenic Biology Interleukin 22 Interferon-gamma Mice Interleukin 20 Psoriasis Drug Discovery medicine Animals Humans Genetics (clinical) Cells Cultured Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha Interleukins Interleukin-17 Interleukin Cell Differentiation Drug Synergism Fibroblasts medicine.disease Immunohistochemistry medicine.anatomical_structure Cytokine Immunology Molecular Medicine Tumor necrosis factor alpha RNA Interference Interleukin 17 Chemokines Epidermis Keratinocyte |
| Zdroj: | Journal of molecular medicine (Berlin, Germany). 87(5) |
| ISSN: | 1432-1440 |
| Popis: | Psoriasis is a common chronic skin disease with a largely unknown pathogenesis. We demonstrate here that transgenic over-expression of interleukin (IL)-22 in mice resulted in neonatal mortality and psoriasis-like skin alterations including acanthosis and hypogranularity. This cutaneous phenotype may be caused by the direct influence of IL-22 on keratinocytes, since this cytokine did not affect skin fibroblasts, endothelial cells, melanocytes, or adipocytes. The comparison of cytokines with hypothesized roles in psoriasis pathogenesis determined that neither interferon (IFN)-gamma nor IL-17, but only IL-22 and, with lower potency, IL-20 caused psoriasis-like morphological changes in a three-dimensional human epidermis model. These changes were associated with inhibited keratinocyte terminal differentiation and with STAT3 upregulation. The IL-22 effect on differentiation-regulating genes was STAT3-dependent. In contrast to IL-22 and IL-20, IFN-gamma and IL-17 strongly induced T-cell and neutrophilic granulocyte-attracting chemokines, respectively. Tumor necrosis factor-alpha potently induced diverse chemokines and additionally enhanced the expression of IL-22 receptor pathway elements and amplified some IL-22 effects. This study suggests that different cytokines are players in the psoriasis pathogenesis although only the IL-10 family members IL-22 and IL-20 directly cause the characteristic epidermal alterations. |
| Databáze: | OpenAIRE |
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