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cAMP inhibits induction of interleukin 2 but not of interleukin 4 in T cells

Novak, Thomas J. and Rothenberg, Ellen V. (1990) cAMP inhibits induction of interleukin 2 but not of interleukin 4 in T cells. Proceedings of the National Academy of Sciences of the United States of America, 87 (23). pp. 9353-9357. ISSN 0027-8424. PMCID PMC55163. https://resolver.caltech.edu/CaltechAUTHORS:20141223-085601805

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Abstract

In this report, we explore the nature of the inductive stimuli leading to expression of the divergently regulated lymphokines interleukin 2 (IL-2) and interleukin 4 (IL-4). Elevation of cAMP levels blocks IL-2 induction while sparing IL-4 induction. These effects are gene-specific, not cell-specific, and can be observed in the same cells. Transient transfection experiments using murine IL-2 regulatory sequences to drive expression of a reporter gene show at least part of the inhibition to act at the transcriptional level. The possible biological significance of these results is indicated by the observation that representative type 2 helper T-cell lines maintain significantly higher levels of cAMP per cell than a type 1 helper T-cell line. Fresh splenic CD4+ T cells, which preferentially make IL-2, have particularly low levels of cAMP per cell and a low capacity to elevate cAMP in response to forskolin. However, their response to forskolin increases significantly after several days of stimulation. These results suggest a potential link between differential cAMP regulation and the divergence of memory T cells into effector subsets.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1073/pnas.87.23.9353DOIArticle
http://www.pnas.org/content/87/23/9353.shortPublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC55163/PubMed CentralArticle
ORCID:
AuthorORCID
Rothenberg, Ellen V.0000-0002-3901-347X
Additional Information:© 2014 National Academy of Sciences. Communicated by Ray D. Owen, September 14, 1990 (received for review June 11, 1990). We thank Dr. Ronald Schwartz and Dr. David Parker, who generously provided the A.E7 and CDC-25 lines; our colleagues Pat White and Dan Chen, for allowing us to cite their unpublished data; Dr. Kim Bottomly, for her initial gift of D10.G4.1 cells and for her continuing interest and patience; Cherrie Leighton, for her fine help with the figures; and Cathy Blagg, for her excellent preparation of the manuscript. This work was supported by a grant from the U.S. Public Health Service (CA39605) to E.V.R.
Funders:
Funding AgencyGrant Number
NIHCA39605
Issue or Number:23
PubMed Central ID:PMC55163
Record Number:CaltechAUTHORS:20141223-085601805
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20141223-085601805
Official Citation:Novak, T. J., & Rothenberg, E. V. (1990). cAMP inhibits induction of interleukin 2 but not of interleukin 4 in T cells. Proceedings of the National Academy of Sciences, 87(23), 9353-9357. doi: 10.1073/pnas.87.23.9353
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:53134
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:23 Dec 2014 19:38
Last Modified:03 Oct 2019 07:47

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