| cAMP antagonizes interleukin 2-promoted T-cell cycle progression at a discrete point in early G1. | |
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MedLine Citation:
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PMID: 2842759 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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T lymphocytes are stimulated to proliferate in an autocrine/paracrine manner by the lymphokine interleukin 2 (IL-2). In seeking further insight into the mechanisms by which IL-2 induces progression of T cells through the G1 phase of the cell cycle, studies were performed with agents that increase cellular adenosine 3',5'-cyclic monophosphate (cAMP), a well-known inhibitor of lymphocyte growth. The addition of dibutyryl-cAMP, cholera toxin, forskolin, or 3-isobutyl-1-methylxanthine to an IL-2-dependent murine T-cell line evoked a dose-related suppression of S-phase transition without affecting cellular viability. Moreover, elevation of cAMP levels led to an accumulation of uniformly small cells, suggesting an arrest in early G1. Consistent with these findings, dibutyryl-cAMP inhibited the incorporation of both [3H]-uridine and [3H]thymidine by IL-2-stimulated, synchronized normal human T cells. Furthermore, maximal inhibition occurred during early G1, as indicated by experiments where the addition of dibutyryl-cAMP was delayed with respect to IL-2 stimulation. Quantitative flow cytometric analysis of RNA and DNA content of IL-2-stimulated cells affirmed that increased cAMP inhibits RNA accumulation and S-phase transition. In addition, exposure of IL-2-dependent, asynchronously proliferating normal human T cells to dibutyryl-cAMP resulted in uniform growth arrest in early G1, the point at which cycling T cells accumulate when they are deprived of IL-2. These results indicate that increased cAMP inhibits G1 progression stimulated by IL-2 and provide a rationale for the use of cAMP analogues as pharmacologic probes for the dissection of molecular events occurring during IL-2 signaling and T-cell G1 transit. They also suggest the possibility of therapeutic immunosuppression by a combination of agents that act at different stages of the T-cell cycle. |
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Authors:
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K W Johnson; B H Davis; K A Smith |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 85 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 1988 Aug |
Date Detail:
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Created Date: 1988-10-05 Completed Date: 1988-10-05 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 6072-6 Citation Subset: IM |
Affiliation:
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Department of Medicine, Dartmouth Medical School, Hanover, NH 03756. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Bucladesine
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pharmacology Cell Division / drug effects Cyclic AMP / physiology* Flow Cytometry Humans Interleukin-2 / pharmacology* Interphase / drug effects* Receptors, Immunologic / analysis Receptors, Interleukin-2 |
| Chemical | |
Reg. No./Substance:
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0/Interleukin-2; 0/Receptors, Immunologic; 0/Receptors, Interleukin-2; 362-74-3/Bucladesine; 60-92-4/Cyclic AMP |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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