Induction of transcription factor AP-2 by inflammatory cytokines in human keratinocytes

Noritaka Oyama, Keiji Iwatsuki, Yoshimi Homma, Fumio Kaneko

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

Activator protein-2 is an important transcription factor for the activation of a number of genes. Here we report the induction of activator protein-2 in response to inflammatory cytokines such as interleukin-6 in keratinocytes. Immunoblotting and semiquantitative reverse transcriptase- polymerase chain reaction assays using normal human keratinocytes revealed that interleukin-6 caused a time- and concentration-dependent induction of activator protein-2 mRNA and protein. The increase of activator protein-2 mRNA was detested at 30 min after stimulation and that of activator protein-2 protein was at 2 h. Their levels were lower than the control levels at 24 h. The interleukin-6-dependent induction of activator protein-2 mRNA was completely blocked by adding actinomycin D, whereas it was ≃ 50% affected by cycloheximide. Coincubation with neutralizing antibodies against various inflammatory cytokines resulted in inhibition of the interleukin-6-dependent activator protein-2 induction at varying degrees, indicating an involvement of various cytokines in the activator protein-2 induction. The activator protein-2 induction was observed in keratinocytes derived from lesional skins with psoriasis or squamous cell carcinoma, and the high levels of activator protein-2 were histochemically detected in these lesions. Furthermore, a gel mobility shift assay using the nuclear extracts from interleukin-6-treated cells showed that interleukin-6 induced the functional activator protein-2 protein for the gene activation. These findings suggest a possible regulation mechanism of activator protein-2 through a complex cytokine system, which is conceivably the initial reaction leading to skin inflammation, and resultant keratinocyte growth and carcinogenesis.

Original languageEnglish
Pages (from-to)600-606
Number of pages7
JournalJournal of Investigative Dermatology
Volume113
Issue number4
DOIs
Publication statusPublished - 1999

Keywords

  • Cell growth
  • Psoriasis
  • Squamous cell carcinoma
  • Transcriptional activation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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