INDUCTION OF TRANSCRIPTION FACTORS IN HUMAN T-LYMPHOCYTES BY ASPIRIN-LIKE DRUGS

Aspirin-like drugs (ALD) induce calcium mobilization, an essential com ponent of T cell activation, but do not induce the biosynthesis of IL- 2. To understand the extent to which ALD may mimic mitogenic stimulati on, we studied cytoplasmic and nuclear signaling steps in ALD-treated T cells. We found that ALD induce a transient activation of protein ki nase (PKC) but have no effect (in comparison to anti-CD3 antibodies) o n protein tyrosine phosphorylation nor on PCL gamma 1 tyrosine phospho rylation. ALD-induced calcium mobilization and PKC activation are inde pendent of tyrosine protein kinase activity as shown by the lack of ef fect of herbimycin, a tyrosine-protein kinase-specific inhibitor. Alth ough we detected no IL-2 mRNA in ALD-treated cells, the nuclei of thes e cells contain proteins capable of binding to three regulatory sequen ces in the IL-2 promoter region: NFAT, NF kappa B, and AP-1. These bin ding activities are expressed only in activated T cells. The expressio n of AP-1 depended on calcium mobilization and PKC activation. These d ata 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 transmi tted to the nucleus and induces DNA-binding activity by several transc ription factors. However, the ALD stimulus is not capable of causing c omplete T cell activation. (C) 1995 Academic Press, Inc.