Abnormal IL-4 gene expression by atopic dermatitis T lymphocytes is reflected in altered nuclear protein interactions with IL-4 transcriptional regulatory element

Sai C. Chan, Melissa A. Brown, Todd M. Willcox, Shi Hua Li, Seth R. Stevens, David Tara, Jon M. Hanifin

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Among the atopic diseases, atopic dermatitis is characterized by the highest levels of serum IgE and by increased peripheral blood T-cell interleukin-4 (IL-4) production. IL-4 promotes IgE synthesis by B cells and stimulates the growth of IL4-producing T cells and may contribute to the pathogenesis of this disease. In this study, in situ hybridization established that atopic dermatitis patients have a higher frequency of IL-4-producing peripheral blood T cell when compared to normal subjects. These in vivo-derived T cells were used to examine the signaling requirements for IL-4 production and the nuclear factors that associate with a critical IL-4 transcriptional regulatory element between -88 and -60 relative to the IL-4 transcription initiation site, the activation responsive element. We demonstrate that, as in T-cell lines, proteins belonging to the NF-AT and AP-1. family of transcription factors are present in stimulated cell extracts and specifically associate with the activation responsive element. Dysregulated IL-4 production is reflected in the nuclear proteins that associate with this element. Using gel shift assays, we found that 12 of 12 nuclear extracts from stimulated atopic T cells formed the activation-dependent protein-DNA complex, compared to only 2 of 12 normal T-cell extracts. Activation complex formation correlated with the relative level of IL-4 mRNA and protein produced in stimulated T cells, suggesting that abnormal IL-4 gene expression in atopic disease may be linked to alterations in nuclear protein interactions with these promoter elements.

Original languageEnglish (US)
Pages (from-to)1131-1136
Number of pages6
JournalJournal of Investigative Dermatology
Volume106
Issue number5
DOIs
StatePublished - Jan 1 1996

Keywords

  • Atopic dermatitis
  • In situ hybridization
  • Transcription factors

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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