Interleukin-4 (IL-4) receptor expression on human T cells is affected by
different intracellular signaling pathways and by IL-4 at transcriptional
and posttranscriptional level
WH Dokter, P Borger, D Hendriks, I van der Horst, MR Halie and E Vellenga
Department of Medicine, University of Groningen, The Netherlands.
Interleukin-4 (IL-4) modulates the survival, proliferation, and
differentiation of a variety of hematopoietic cells. The effects are
mediated through a single class of high-affinity receptors for IL-4. To
understand the biologic effects of IL-4 on human T cells, we studied the
regulation of IL-4 receptor (IL-4R) gene expression. We showed that IL-4R
mRNA accumulation in human T cells is enhanced fourfold after activation of
different secondary signaling pathways by concanavalin A (Con A), phorbol
myristate acetate (PMA), the calcium ionophore A23187, and combinations of
these factors. This could be ascribed to an increase in the IL-4R
transcription rate and to stabilization of IL-4R mRNA resulting in a
half-life of 80 to 90 minutes (v 35 to 40 minutes in resting T cells). IL-4
did enhance the IL-4R mRNA accumulation by a factor 10, which was caused by
an increase in the IL-4R transcription rate and prolonging the half-life of
IL-4R transcripts to 140 to 160 minutes. Finally, it was shown that A23187
induced IL-4R mRNA expression is a protein synthesis-dependent process. In
contrast, Con A- , PMA-, Con A + PMA-, and Con A + A23187-induced
expression of IL-4R mRNA is protein-synthesis independent. Cyclosporine A
inhibited the A23187- and Con A + A23187-induced IL-4R mRNA accumulation,
whereas Con A-, PMA-, and Con A + PMA-induced IL-4R mRNA expression was not
affected by this drug. These data indicate that expression of IL-4
receptors on human T cells can be modulated by different intracellular
signaling pathways at both transcriptional and posttranscriptional levels.
Volume 80,
Issue 11,
pp. 2721-2728,
12/01/1992
Copyright © 1992 by The American Society of Hematology
