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IRF-1 expression in normal human epidermal keratinocytes

G Nakanishi1, W Fujimoto, J Arata

  • 1Department of Dermatology, Okayama University Medical School, Japan.

Archives of Dermatological Research
|June 1, 1997
PubMed
Summary

Interferon gamma (IFN-gamma) induces Interferon regulatory factor-1 (IRF-1) mRNA in skin cells. This induction is a direct gene transcription process, independent of protein synthesis or protein kinase C signaling.

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Area of Science:

  • Molecular Biology
  • Dermatology
  • Immunology

Background:

  • Interferon gamma (IFN-gamma) inhibits cell growth in human epidermal keratinocytes.
  • Interferon regulatory factor-1 (IRF-1) mediates IFN-gamma effects and may act as a tumor suppressor.
  • IRF-1's role in IFN-gamma's antiproliferative action warrants investigation.

Purpose of the Study:

  • To investigate the expression of IRF-1 mRNA in normal human epidermal keratinocytes (NHEK).
  • To determine the regulatory mechanism of IFN-gamma-induced IRF-1 mRNA expression.

Main Methods:

  • Northern blot analysis was used to detect IRF-1 mRNA levels.
  • Experiments involved treatments with IFN-gamma, cycloheximide, actinomycin D, TPA, and H7.
  • Cellular responses were assessed in normal human epidermal keratinocytes (NHEK).

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Main Results:

  • IFN-gamma significantly increased IRF-1 mRNA expression in NHEKs.
  • The induction of IRF-1 mRNA by IFN-gamma was resistant to cycloheximide but sensitive to actinomycin D.
  • Neither protein kinase C (PKC) activation (TPA) nor inhibition (H7) altered IFN-gamma's effect on IRF-1 mRNA induction.

Conclusions:

  • IFN-gamma-induced IRF-1 mRNA expression in NHEKs is regulated at the transcriptional level.
  • The induction mechanism is independent of protein synthesis and protein kinase C signaling pathways.