Induction of transcription factors in human T lymphocytes by aspirin-like drugs

Eliezer Flescher, Jeffrey A. Ledbetter, Noryoshi Ogawa, Norma Vela-Roch, Donna Fossum, Howard Dang, Norman Talal

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Aspirin-like drugs (ALD) induce calcium mobilization, an essential component of T cell activation, but do not induce the biosynthesis of IL-2. To understand the extent to which ALD may mimic mitogenic stimulation, we studied cytoplasmic and nuclear signaling steps in ALD-treated T cells. We found that ALD induce a transient activation of protein kinase (PKC) but have no effect (in comparison to anti-CD3 antibodies) on protein tyrosine phosphorylation nor on PCLγ1 tyrosine phosphorylation. ALD-induced calcium mobilization and PKC activation are independent of tyrosine protein kinase activity as shown by the lack of effect of herbimycin, a tyrosine-protein kinase-specific inhibitor. Although we detected no IL-2 mRNA in ALD-treated cells, the nuclei of these cells contain proteins capable of binding to three regulatory sequences in the IL-2 promoter region: NFAT, NFκB, and AP-1. These binding activities are expressed only in activated T cells. The expression of AP-1 depended on calcium mobilization and PKC activation. These data suggest that ALD cause transient but significant changes in T cell transmembrane signaling, although some events induced by stimulation with anti-CD3 antibodies are not induced by ALD. The signal is transmitted to the nucleus and induces DNA-binding activity by several transcription factors. However, the ALD stimulus is not capable of causing complete T cell activation.

Original languageEnglish (US)
Pages (from-to)232-239
Number of pages8
JournalCellular Immunology
Volume160
Issue number2
DOIs
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • Immunology

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