Negative regulation of interleukin-2 production in primary lymphocytes by 12-O-tetradecanoylphorbol-13-acetate

A. M. Mastro, C. G. Garlisi, D. S. Grove, C. E. Grier, S. A. Pishak

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Stimulation of quiescent T lymphocytes to proliferate involves a complex series of events both between and within cells. At least 70 genes are known to be induced or activated from the time of the initial stimulation until DNA synthesis. While some of these gene products, e.g., interleukin-2 (IL-2) and IL-2 receptors, are required for proliferation, others, e.g., γ-interferon and colony-stimulating factor, are ancillary to activated T cell function. Several biochemical signal transductions are among the early events. One of the earliest is phospholipase C-mediated hydrolysis of phosphatidylinositol leading to release of diacylglycerols and inositol phosphates, which in turn activate protein kinase C and elevate intracellular free calcium levels. The discovery that the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) both enhances proliferation and activates protein kinase C strengthens the evidence for a general role of protein kinase C in proliferation. Yet, the exact consequences of stimulation of protein kinase C in regard to specific proliferation proteins is still not clear. In this study, we present evidence that protein kinase C activation is directed to production of IL-2 but not to IL-2 receptors. Under conditions of TPA treatment in which protein kinase C was chronically reduced in T lymphocytes, IL-2 production was greatly depressed as were the level of IL-2 mRNA and [3H]thymidine incorporation. In contrast, these cells still expressed high affinity IL-2 receptors and proliferated when endogenous IL-2 was added. Because neither phosphatidylinositol metabolism nor Ca2+ flux was affected, the block appeared to be mediated directly or indirectly through protein kinase C.

Original languageEnglish (US)
Pages (from-to)153-164
Number of pages12
JournalLymphokine and Cytokine Research
Volume10
Issue number3
StatePublished - 1991

Fingerprint

Tetradecanoylphorbol Acetate
Protein Kinase C
Interleukin-2
Lymphocytes
Interleukin-2 Receptors
Phosphatidylinositols
T-Lymphocytes
Colony-Stimulating Factors
Inositol Phosphates
Diglycerides
Type C Phospholipases
Phorbol Esters
Thymidine
Interferons
Genes
Signal Transduction
Hydrolysis
Calcium
Messenger RNA
DNA

All Science Journal Classification (ASJC) codes

  • Immunology
  • Hematology

Cite this

Mastro, A. M., Garlisi, C. G., Grove, D. S., Grier, C. E., & Pishak, S. A. (1991). Negative regulation of interleukin-2 production in primary lymphocytes by 12-O-tetradecanoylphorbol-13-acetate. Lymphokine and Cytokine Research, 10(3), 153-164.
Mastro, A. M. ; Garlisi, C. G. ; Grove, D. S. ; Grier, C. E. ; Pishak, S. A. / Negative regulation of interleukin-2 production in primary lymphocytes by 12-O-tetradecanoylphorbol-13-acetate. In: Lymphokine and Cytokine Research. 1991 ; Vol. 10, No. 3. pp. 153-164.
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Mastro, AM, Garlisi, CG, Grove, DS, Grier, CE & Pishak, SA 1991, 'Negative regulation of interleukin-2 production in primary lymphocytes by 12-O-tetradecanoylphorbol-13-acetate', Lymphokine and Cytokine Research, vol. 10, no. 3, pp. 153-164.

Negative regulation of interleukin-2 production in primary lymphocytes by 12-O-tetradecanoylphorbol-13-acetate. / Mastro, A. M.; Garlisi, C. G.; Grove, D. S.; Grier, C. E.; Pishak, S. A.

In: Lymphokine and Cytokine Research, Vol. 10, No. 3, 1991, p. 153-164.

Research output: Contribution to journalArticle

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T1 - Negative regulation of interleukin-2 production in primary lymphocytes by 12-O-tetradecanoylphorbol-13-acetate

AU - Mastro, A. M.

AU - Garlisi, C. G.

AU - Grove, D. S.

AU - Grier, C. E.

AU - Pishak, S. A.

PY - 1991

Y1 - 1991

N2 - Stimulation of quiescent T lymphocytes to proliferate involves a complex series of events both between and within cells. At least 70 genes are known to be induced or activated from the time of the initial stimulation until DNA synthesis. While some of these gene products, e.g., interleukin-2 (IL-2) and IL-2 receptors, are required for proliferation, others, e.g., γ-interferon and colony-stimulating factor, are ancillary to activated T cell function. Several biochemical signal transductions are among the early events. One of the earliest is phospholipase C-mediated hydrolysis of phosphatidylinositol leading to release of diacylglycerols and inositol phosphates, which in turn activate protein kinase C and elevate intracellular free calcium levels. The discovery that the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) both enhances proliferation and activates protein kinase C strengthens the evidence for a general role of protein kinase C in proliferation. Yet, the exact consequences of stimulation of protein kinase C in regard to specific proliferation proteins is still not clear. In this study, we present evidence that protein kinase C activation is directed to production of IL-2 but not to IL-2 receptors. Under conditions of TPA treatment in which protein kinase C was chronically reduced in T lymphocytes, IL-2 production was greatly depressed as were the level of IL-2 mRNA and [3H]thymidine incorporation. In contrast, these cells still expressed high affinity IL-2 receptors and proliferated when endogenous IL-2 was added. Because neither phosphatidylinositol metabolism nor Ca2+ flux was affected, the block appeared to be mediated directly or indirectly through protein kinase C.

AB - Stimulation of quiescent T lymphocytes to proliferate involves a complex series of events both between and within cells. At least 70 genes are known to be induced or activated from the time of the initial stimulation until DNA synthesis. While some of these gene products, e.g., interleukin-2 (IL-2) and IL-2 receptors, are required for proliferation, others, e.g., γ-interferon and colony-stimulating factor, are ancillary to activated T cell function. Several biochemical signal transductions are among the early events. One of the earliest is phospholipase C-mediated hydrolysis of phosphatidylinositol leading to release of diacylglycerols and inositol phosphates, which in turn activate protein kinase C and elevate intracellular free calcium levels. The discovery that the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) both enhances proliferation and activates protein kinase C strengthens the evidence for a general role of protein kinase C in proliferation. Yet, the exact consequences of stimulation of protein kinase C in regard to specific proliferation proteins is still not clear. In this study, we present evidence that protein kinase C activation is directed to production of IL-2 but not to IL-2 receptors. Under conditions of TPA treatment in which protein kinase C was chronically reduced in T lymphocytes, IL-2 production was greatly depressed as were the level of IL-2 mRNA and [3H]thymidine incorporation. In contrast, these cells still expressed high affinity IL-2 receptors and proliferated when endogenous IL-2 was added. Because neither phosphatidylinositol metabolism nor Ca2+ flux was affected, the block appeared to be mediated directly or indirectly through protein kinase C.

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