Regulation of interleukin-13 by type 4 cyclic nucleotide phosphodiesterase (PDE) inhibitors in allergen-specific human T lymphocyte clones

David M. Essayan, Anne Kagey-Sobotka, Lawrence M. Lichtenstein, Shau Ku Huang

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Interleukin-13 (IL-13) is a proinflammatory cytokine of T cell origin. Structural and functional studies suggest a key role for IL-13 in the genesis of chronic allergic inflammation; as such, its pharmacologic inhibition is of potential clinical utility. We studied the pharmacologic regulation of IL- 13 expression by cyclic nucleotide phosphodiesterase (PDE) inhibitors in a panel of Amb a 1 (a major allergen of short ragweed, Ambrosia artemisiifolia)- specific T cell clones derived from a ragweed allergic, asthmatic subject. Proliferative responses of these cells were down-regulated by rolipram, a PDE4 inhibitor (% inhibition(MAX) = 67%; IC50 = 20 μM). While the PDE3 inhibitor siguazodan provided no independent efficacy (IC50 > 10-4 M), an increased efficacy of rolipram m the presence of 10-5 M siguazodan was noted at 10-6, 10-5, and 10-4 M rolipram (P < 0.03, 0.01, and 0.04, respectively). The EC50 values remained unchanged between assays using the PDE4 inhibitor with or without the PDE3 inhibitor. Both IL-13 gene expression and protein secretion into culture supernatants were down-regulated by the PDE4 inhibitor (P ≤ 0.005). Once again, the use of a PDE3 inhibitor provided no independent efficacy (P ≤ 0.2), and in this instance, increased efficacy of the PDE4 inhibitor with the PDE3 inhibitor was not apparent (P ≤ 0.3). IL-13 production from clones with Th0, Th1, and Th2 phenotypes appeared equally sensitive to treatment with the PDE4 inhibitor. We conclude that the anti-inflammatory effects of PDE4 inhibitors may be mediated, in part, by down-regulation of IL-13.

Original languageEnglish
Pages (from-to)1055-1060
Number of pages6
JournalBiochemical Pharmacology
Volume53
Issue number7
DOIs
Publication statusPublished - Apr 4 1997
Externally publishedYes

Fingerprint

Type 4 Cyclic Nucleotide Phosphodiesterase
Phosphodiesterase 4 Inhibitors
Phosphodiesterase Inhibitors
T-cells
Interleukin-13
Phosphodiesterase 3 Inhibitors
Interleukin-4
Allergens
Clone Cells
Rolipram
T-Lymphocytes
Ambrosia
Inhibitory Concentration 50
Cyclic Nucleotides
Gene expression
Assays
Anti-Inflammatory Agents
Down-Regulation
Cytokines
Inflammation

Keywords

  • allergy
  • cAMP
  • human
  • interleukin-13
  • phosphodiesterase
  • T lymphocyte

ASJC Scopus subject areas

  • Pharmacology

Cite this

Regulation of interleukin-13 by type 4 cyclic nucleotide phosphodiesterase (PDE) inhibitors in allergen-specific human T lymphocyte clones. / Essayan, David M.; Kagey-Sobotka, Anne; Lichtenstein, Lawrence M.; Huang, Shau Ku.

In: Biochemical Pharmacology, Vol. 53, No. 7, 04.04.1997, p. 1055-1060.

Research output: Contribution to journalArticle

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abstract = "Interleukin-13 (IL-13) is a proinflammatory cytokine of T cell origin. Structural and functional studies suggest a key role for IL-13 in the genesis of chronic allergic inflammation; as such, its pharmacologic inhibition is of potential clinical utility. We studied the pharmacologic regulation of IL- 13 expression by cyclic nucleotide phosphodiesterase (PDE) inhibitors in a panel of Amb a 1 (a major allergen of short ragweed, Ambrosia artemisiifolia)- specific T cell clones derived from a ragweed allergic, asthmatic subject. Proliferative responses of these cells were down-regulated by rolipram, a PDE4 inhibitor ({\%} inhibition(MAX) = 67{\%}; IC50 = 20 μM). While the PDE3 inhibitor siguazodan provided no independent efficacy (IC50 > 10-4 M), an increased efficacy of rolipram m the presence of 10-5 M siguazodan was noted at 10-6, 10-5, and 10-4 M rolipram (P < 0.03, 0.01, and 0.04, respectively). The EC50 values remained unchanged between assays using the PDE4 inhibitor with or without the PDE3 inhibitor. Both IL-13 gene expression and protein secretion into culture supernatants were down-regulated by the PDE4 inhibitor (P ≤ 0.005). Once again, the use of a PDE3 inhibitor provided no independent efficacy (P ≤ 0.2), and in this instance, increased efficacy of the PDE4 inhibitor with the PDE3 inhibitor was not apparent (P ≤ 0.3). IL-13 production from clones with Th0, Th1, and Th2 phenotypes appeared equally sensitive to treatment with the PDE4 inhibitor. We conclude that the anti-inflammatory effects of PDE4 inhibitors may be mediated, in part, by down-regulation of IL-13.",
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