Polymorphisms in the interferon regulatory factor-1 promoter are not associated with psoriasis and do not influence IFN-α-induced Th1 polarization
Journal of Interferon and Cytokine Research , Volume 27 - Issue 10 p. 841- 846
Psoriasis is a chronic inflammatory skin disease, characterized by a Th1 cytokine profile. We previously demonstrated that type I interferon (IFN-α/β) 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-α responses. IFN-α stimulation caused a similar enhancement of IFN-γ and interleukin-10 (IL-10) secretion in psoriasis patients and controls, although the level of induction was variable. It was previously suggested that IFN-α-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-γ 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-α-induced Th1 polarization. We further demonstrate that psoriatic PBMCs do not respond aberrantly to IFN-α with respect to the production of the proinflammatory IFN-γ and the anti-inflammatory IL-10.
|Journal of Interferon and Cytokine Research|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
van der Fits, L, Kant, M, van der Wel, L.I, & Prens, E.P. (2007). Polymorphisms in the interferon regulatory factor-1 promoter are not associated with psoriasis and do not influence IFN-α-induced Th1 polarization. Journal of Interferon and Cytokine Research, 27(10), 841–846. doi:10.1089/jir.2007.0013