Prominent Production of IL-20 by CD68+/CD11c+ Myeloid-Derived Cells in Psoriasis: Gene Regulation and Cellular Effects
| Autor: | Edmund Lee, Michelle A. Lowes, Judilyn Fuentes-Duculan, Frank Wang, Irma Cardinale, Asifa Haider, Francesca Chamian, James G. Krueger, Maria Veronica Abello |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Adult
Keratinocytes Integrin beta Chains Recombinant Fusion Proteins medicine.medical_treatment CD2 Antigens Antigens Differentiation Myelomonocytic Alefacept Inflammation Dermatology Biology Biochemistry Monocytes Interferon-gamma 030207 dermatology & venereal diseases 03 medical and health sciences 0302 clinical medicine Interleukin 20 Downregulation and upregulation Antigens CD Psoriasis Leukocytes medicine Humans RNA Messenger Receptor Molecular Biology Oligonucleotide Array Sequence Analysis Skin 030304 developmental biology 0303 health sciences Tumor Necrosis Factor-alpha Interleukins Receptors Interleukin Cell Biology medicine.disease CD11c Antigen medicine.anatomical_structure Cytokine Gene Expression Regulation Immunology Cancer research Tumor necrosis factor alpha medicine.symptom Keratinocyte |
| Zdroj: | Journal of Investigative Dermatology. 126(7):1590-1599 |
| ISSN: | 0022-202X |
| DOI: | 10.1038/sj.jid.5700310 |
| Popis: | We assessed expression of IL-20 and its receptors in psoriasis, given the recent implication of IL-20 in epidermal hyperplasia. Psoriatic lesional (LS) skin consistently expressed more IL-20 mRNA than nonlesional (NL) skin. Immunoreactivity to IL-20 protein was greater in LS tissue and mainly localized to infiltrating CD68 + /CD11c + (myeloid-derived) dermal leukocytes. Because this contrasted with earlier reports of a keratinocyte source, we assessed IL-20 mRNA expression in a variety of cells in vitro , and confirmed a myeloid-derived cellular source (monocytes). Plastic adhesion, activation of β 2 integrins, and incubation with tumor necrosis factor- α stimulated expression in these cells. IL-20 receptor (IL-20R) α and IL-20R β mRNA was decreased in LS versus NL skin, which also contrasted with earlier findings. To investigate the relationship between IL-20 and disease activity, we examined psoriasis patients treated with the CD2-targeted agent alefacept. In therapeutic responders, lesional IL-20 mRNA decreased to NL levels, suggesting that CD2 + leukocytes may proximally regulate IL-20. Finally, to assess IL-20 function, we used microarrays to screen IL-20-treated keratinocytes, which demonstrated upregulation of disease-related and IFN- γ -induced genes. Hence, IL-20 may influence inflammation through IFN-like effects. Together, these data indicate that IL-20 may be an important effector cytokine in psoriasis, and that its inhibition may represent a potential therapeutic target. |
| Databáze: | OpenAIRE |
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