c-Rel is a target of pentoxifylline-mediated inhibition of T lymphocyte activation

Weihong Wang, Winnie F. Tam, Christopher C W Hughes, Satyajit Rath, Ranjan Sen

Research output: Contribution to journalArticlepeer-review

Abstract

The possible clinical use of the methyl xanthine derivative, pentoxifylline (PF), for the treatment of T cell-dependent diseases is being noted with increasing interest. In this paper, we studied the molecular consequences of PF treatment during lymphocyte activation. We found that in T cells, anti-CD3-induced c-Rel expression was blocked by PF, whereas the induction of other NF-κB family members was not significantly affected. However, induction of NF-AT, which has the same signaling requirements as c-Rel induction, was not inhibited by PF. Among genes that respond to these transcription factors, IL-2 mRNA induction was suppressed by PF, whereas IL-2Rα chain mRNA induction was not affected. These observations implicated c-Rel as an IL-2 promoter factor, for which experimental support was obtained from transient transfection experiments. In contrast with the observation in T cells, c-Rel induction was not blocked by PF in B cells. The greater selectivity of PF, compared with FK506, at both the molecular and cellular levels may prove advantageous in manipulating T cell responses in vivo.

Original languageEnglish (US)
Pages (from-to)165-174
Number of pages10
JournalImmunity
Volume6
Issue number2
DOIs
StatePublished - Feb 1997
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

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