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Expression and regulation of mRNA for distinct isoforms of cAMP-specific PDE-4 in mitogen-stimulated and leukemic human lymphocytes

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Abstract

We reported previously that the gene for PDE-1B1 is induced in isolated human peripheral blood lymphocytes (HPBL) following mitogenic stimulation (Jiang, X., Li, J., Paskind, M., and Epstein, P. M. [1996]Proc. Natl. Acad. Sci. USA 93, 11,236–11,241). Using reverse transcription-polymerase chain reaction (RT-PCR), we investigated possible changes in the expression of the four genes for cAMP-specific phosphodiesterase (PDE-4A-D) in HPBL under the same conditions. Isolated, quiescent HPBL express mRNA for PDE-4B as the principal transcript. Following mitogenic stimulation with phytohemagglutinin (PHA), mRNA for PDE-4A and PDE-4D are clearly induced. HPBL appear not to express PDE-4C under resting or stimulated conditions. The PHA induced increase in PDE-1B1, PDE-4A, and PDE-4D mRNA is mimicked by incubation of HPBL with dibutyryl cAMP (dBcAMP) and 1-methyl-3-isobutylxanthine (IBMX). The B-lymphoblastoid cell line, RPMI 8392, and the T-leukemic cell line, Molt 4, express PDE-4A mRNA as the most abundant transcript, but incubation with dBcAMP and IBMX induces an increase in the expression of mRNA for PDE-4B in both of these cell lines, and in PDE-4D3 in the RPMI 8392 cell line. These studies demonstrate that expression of mRNA for PDE-1B1 and some of the subtypes of PDE-4 are induced in HPBL following mitogenic stimulation, possibly secondarily to elevation of cAMP induced by the mitogen. As already indicated for PDE-1B1, some of these subtypes of PDE-4 might also provide additional therapeutic targets for treatment of immunoproliferative disorders and immune dysfunction.

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Abbreviations

PDE:

cyclic nucleotide phosphodiesterase

HPBL:

human peripheral blood lymphocytes

HPBM:

human peripheral blood monocytes

RT-PCR:

reverse transcription-polymerase chain reaction

CaM:

calmodulin

PHA:

phytohemagglutinin

Con A:

concanavalin A

PMA:

phorbol myristic acid

PKA:

cAMP-dependent protein kinase

PKC:

protein kinase C

CRE:

cAMP-response element

CREB:

cAMP-response element binding proteins

dBcAMP:

dibutyryl cAMP

8-Br-cAMP:

8-bromo-cAMP

IBMX:

1-methyl-3-isobutylxanthine

FSH:

follicle-stimulating hormone

TSH:

thyroid-stimulating hormone

SDS-PAGE:

sodium dodecyl sulfate-polyacrylamide gel electrophoresis

nt:

nucleotide(s)

bp:

base pair(s)

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Authors and Affiliations

  1. Department of Pharmacology, University of Connecticut Health Center, 06030, Farmington, CT

    Xin Jiang, Robert Weltzien & Paul M. Epstein

  2. BASF Bioresearch Corporation, Worcester, MA

    Michael Paskind

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  1. Xin Jiang
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  2. Michael Paskind
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  3. Robert Weltzien
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  4. Paul M. Epstein
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Correspondence to Paul M. Epstein.

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Jiang, X., Paskind, M., Weltzien, R. et al. Expression and regulation of mRNA for distinct isoforms of cAMP-specific PDE-4 in mitogen-stimulated and leukemic human lymphocytes. Cell Biochem Biophys 28, 135–160 (1998). https://doi.org/10.1007/BF02737809

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  • DOI: https://doi.org/10.1007/BF02737809

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