cAMP inducibility of transcriptional repressor ICER in developing and mature human T lymphocytes.

We show that elevated cAMP levels in T cells correlate with the expression of the potent transcriptional repressor ICER previously described in the hypothalamicpituitary-gonadal axis

J. Bodor; A. L. Spetz; J. L. Strominger; J. F. Habener

2002

Scholarcy highlights

  • Stimulation of the cAMP-dependent signaling pathway exerts an inhibitory effect on the proliferation and effector functions of T cells
  • Because of the known circadian fluctuations in the proliferation and activities of lymphocytes, we sought to determine whether high levels of intracellular cAMP in developing T lymphocytes could induce the expression of inducible cAMP early repressor and so implicate a potential role for ICER in the observed inhibitory effects of cAMP on mature T cells
  • Inasmuch as IL-2 is critical for the proliferation of T cells, these findings suggest that the induction of the ICER may be a mechanism to explain the antiproliferative effects of cAMP signaling on T cells
  • The 5' and 3' primers were selected to begin with the start codon and stop codon, Abbreviations: ICER, inducible cAMP early repressor; IL-2, interleukin 2; HTLV-I, human T-lymphotropic virus type I; PGE2, prostaglandin E2; PBL, peripheral blood lymphocyte; bZIP, basic leucine zipper; PKA, protein kinase A; CRE, cAMP response element; PMA, phorbol 12myristate 13-acetate. §To whom reprint requests should be addressed at: Laboratory of Molecular Endocrinology, Massachusetts General Hospital, WEL 320, Boston, MA 02114
  • PGE2 or forskolin markedly stimulated cAMP levels in mature PBL T cells, whereas little or no response was observed in B cells
  • These large differences in the responses of separated thymocytes led us to examine whether the elevations of cAMP that are measured in medullary thymocytes and mature PBL T cells could be sufficient to induce the transcriptional repressor ICER
  • Construction of RNase protection probes specific for the detection of inducible cAMP early repressor mRNAs expressed in thymocytes

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