Polymorphisms in the interferon regulatory factor-1 promoter are not associated with psoriasis and do not influence IFN-alpha-induced Th1 polarization
| Autor: | Marius Kant, Leontine I van der Wel, Errol P. Prens, Leslie van der Fits |
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| Přispěvatelé: | Dermatology, Immunology |
| Rok vydání: | 2007 |
| Předmět: |
Immunology
Single-nucleotide polymorphism Biology Peripheral blood mononuclear cell Polymorphism Single Nucleotide Proinflammatory cytokine Interferon Virology Psoriasis medicine Humans Secretion Genetic Predisposition to Disease Promoter Regions Genetic Transcription factor Interferon-alpha Cell Biology Th1 Cells medicine.disease Interleukin-10 IRF1 Cancer research medicine.drug Interferon Regulatory Factor-1 |
| Zdroj: | Journal of Interferon and Cytokine Research, 27(10), 841-846. Mary Ann Liebert Inc. |
| ISSN: | 1079-9907 |
| Popis: | Psoriasis is a chronic inflammatory skin disease, characterized by a Th1 cytokine profile. We previously demonstrated that type I interferon (IFN-alpha/beta) signaling is activated in psoriatic skin. Type I IFNs regulate the expression of many proinflammatory and anti-inflammatory cytokines, resulting in Th1 polarization. We assessed whether peripheral blood mononuclear cells (PBMC) from psoriatic patients show aberrant IFN-alpha responses. IFN-alpha stimulation caused a similar enhancement of IFN-gamma and interleukin-10 (IL-10) secretion in psoriasis patients and controls, although the level of induction was variable. It was previously suggested that IFN-alpha-induced Th1 polarization is influenced by single nucleotide polymorphisms (SNPs) in the promoter of IFN regulatory factor-1 (IRF-1), a transcription factor involved in IFN signaling, providing a putative explanation for the observed variation. However, sequence analysis revealed no correlation between SNPs in the IRF-1 promoter and induction of IFN-gamma or IL-10 expression. Furthermore, the frequency of the SNPs and psoriasis were not linked. Our data demonstrate that the described IRF-1 promoter SNPs do not play a role in the pathogenesis of psoriasis or in influencing IFN-alpha-induced Th1 polarization. We further demonstrate that psoriatic PBMCs do not respond aberrantly to IFN-alpha with respect to the production of the proinflammatory IFN-gamma and the anti-inflammatory IL-10. |
| Databáze: | OpenAIRE |
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