title: Polymorphisms in the interferon regulatory factor-1 promoter are not associated with psoriasis and do not influence IFN-alpha-induced Th1 polarization.
abstract: 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.
authors.affiliation: Department of Immunology, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Leslie
authors.initials: L
authors.lastname: Van Der Fits
authors.forename: Marius
authors.initials: M
authors.lastname: Kant
authors.forename: Leontine I
authors.initials: LI
authors.lastname: Van Der Wel
authors.forename: Errol P
authors.initials: EP
authors.lastname: Prens
mesh_terms: D020022:Genetic Predisposition to Disease; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000235:genetics*; D016898:Interferon-alpha / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology / Q000494:pharmacology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011565:Psoriasis / Q000235:genetics*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*
chemical_list: D050856:Interferon Regulatory Factor-1; D016898:Interferon-alpha; D016753:Interleukin-10