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In psoriasis lesional skin the type I interferon signaling pathway is activated, whereas interferon-alpha sensitivity is unaltered.

Abstract
The epidermal phenotype as observed in psoriatic skin results from inflammation and abnormal proliferation and terminal differentiation of keratinocytes. Mice deficient for interferon regulatory factor-2, a repressor of interferon signaling, display psoriasis-like skin inflammation. The development of this phenotype is strictly dependent on type I interferon (interferon-alpha/beta) signaling. The aim of this study was to assess the involvement of interferon-alpha/beta in the pathogenesis of human psoriasis. In psoriatic skin, we measured an increased expression of components that play central and crucial roles in interferon-alpha/beta signal transduction. Culturing keratinocytes or healthy skin biopsies with recombinant interferon-alpha stimulated this signaling pathway; however, this did not induce the expression of markers that are generally used to define the psoriasis phenotype. Furthermore, skin from psoriasis patients responded identically to interferon-alpha stimulation, demonstrating that psoriatic skin does not have an aberrant sensitivity to type I interferon. We conclude that in psoriatic lesional skin the type I interferon signaling pathway is activated, despite an unaltered interferon-alpha sensitivity. Our data furthermore show that type I interferon, in contrast to interferon-gamma, does not act directly on keratinocytes to induce a psoriatic phenotype. Thus, if the observed activated type I interferon signaling is indeed functionally involved in the pathogenesis of psoriasis, its contribution might be indirect, putatively involving other cell types besides keratinocytes.
AuthorsLeslie van der Fits, Leontine I van der Wel, Jon D Laman, Errol P Prens, Martie C M Verschuren
JournalThe Journal of investigative dermatology (J Invest Dermatol) Vol. 122 Issue 1 Pg. 51-60 (Jan 2004) ISSN: 0022-202X [Print] United States
PMID14962089 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • DNA-Binding Proteins
  • IRF7 protein, human
  • IRF9 protein, human
  • Interferon Regulatory Factor-7
  • Interferon-Stimulated Gene Factor 3
  • Interferon-Stimulated Gene Factor 3, gamma Subunit
  • Interferon-alpha
  • RNA, Messenger
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Trans-Activators
  • Transcription Factors
  • Interferon-beta
Topics
  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents (metabolism, pharmacology)
  • Biopsy
  • Cell Nucleus (metabolism)
  • Cells, Cultured
  • DNA-Binding Proteins (genetics, metabolism)
  • Female
  • Gene Expression (immunology)
  • Humans
  • Interferon Regulatory Factor-7
  • Interferon-Stimulated Gene Factor 3
  • Interferon-Stimulated Gene Factor 3, gamma Subunit
  • Interferon-alpha (metabolism, pharmacology)
  • Interferon-beta (metabolism, pharmacology)
  • Keratinocytes (cytology, metabolism)
  • Male
  • Middle Aged
  • Phenotype
  • Psoriasis (metabolism, pathology)
  • RNA, Messenger (analysis)
  • STAT1 Transcription Factor
  • Signal Transduction (drug effects, physiology)
  • Trans-Activators (metabolism)
  • Transcription Factors (metabolism)

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