Effect of theophylline and specific phosphodiesterase IV inhibition on proliferation and apoptosis of progenitor cells in bronchial asthma

Chun Hua Wang, Horng Chyuan Lin, Chien-Huang Lin, Chih Teng Yu, Su Ling Liu, Kuo Hsiung Huang, Kian Fan Chung, Han Pin Kuo

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

1. Theophylline possesses anti-inflammatory activities in asthma. We examined whether theophylline and agents that modulate cyclic AMP can determine the survival and proliferation of progenitor cells. 2. Progenitor cells from the blood of normal and asthmatic subjects were cultured for 14 days in methylcellulose with GM-CSF, stem cell factor, IL-3 and IL-5. Apoptosis was measured by flow cytometry of propidium-iodide-stained cells. 3. A greater number of colonies with a higher proportion of cells of eosinophil lineage from asthmatics compared to normal subjects were grown. Theophylline (at 5 and 20 μg ml -1) significantly inhibited colony formation and increased apoptotic cells in asthmatics compared to control. Salbutamol (0.1, 1, 10 μM), dibutyryl-cAMP (0.1, 1 mM) and rolipram (0.1, 1 mM), a phosphodiesterase IV inhibitor, also dose-dependently decreased colony numbers and increased apoptosis of progenitor cells from asthmatics. 4. There was no significant effect of theophylline, db-cAMP, salbutamol or rolipram on colony formation or the survival of progenitor cells from normal subjects. AMP did not affect the colony formation and apoptosis. Expression of Bcl-2 protein on progenitor cells of asthma was downregulated by theophylline, salbutamol, db-cAMP and rolipram. 5. Theophylline and rolipram decreased colony formation committed to the eosinophil lineage, together with an increase in apoptosis through an inhibition of Bcl-2 expression effects that may occur through cAMP. The anti-inflammatory properties of theophylline include an inhibition of circulating progenitor cells.

Original languageEnglish
Pages (from-to)1147-1155
Number of pages9
JournalBritish Journal of Pharmacology
Volume138
Issue number6
DOIs
Publication statusPublished - Mar 2003

Fingerprint

Type 4 Cyclic Nucleotide Phosphodiesterase
Theophylline
Rolipram
Stem Cells
Asthma
Apoptosis
Albuterol
Eosinophils
Anti-Inflammatory Agents
Methylcellulose
Stem Cell Factor
Phosphodiesterase Inhibitors
Propidium
Interleukin-3
Interleukin-5
Cell Lineage
Adenosine Monophosphate
Granulocyte-Macrophage Colony-Stimulating Factor
Cyclic AMP
Flow Cytometry

Keywords

  • Apoptosis
  • Asthma
  • Bcl-2 protein
  • CD34 + progenitor cells
  • Phosphodiesterase inhibition
  • Theophylline

ASJC Scopus subject areas

  • Pharmacology

Cite this

Effect of theophylline and specific phosphodiesterase IV inhibition on proliferation and apoptosis of progenitor cells in bronchial asthma. / Wang, Chun Hua; Lin, Horng Chyuan; Lin, Chien-Huang; Yu, Chih Teng; Liu, Su Ling; Huang, Kuo Hsiung; Chung, Kian Fan; Kuo, Han Pin.

In: British Journal of Pharmacology, Vol. 138, No. 6, 03.2003, p. 1147-1155.

Research output: Contribution to journalArticle

Wang, Chun Hua ; Lin, Horng Chyuan ; Lin, Chien-Huang ; Yu, Chih Teng ; Liu, Su Ling ; Huang, Kuo Hsiung ; Chung, Kian Fan ; Kuo, Han Pin. / Effect of theophylline and specific phosphodiesterase IV inhibition on proliferation and apoptosis of progenitor cells in bronchial asthma. In: British Journal of Pharmacology. 2003 ; Vol. 138, No. 6. pp. 1147-1155.
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AU - Wang, Chun Hua

AU - Lin, Horng Chyuan

AU - Lin, Chien-Huang

AU - Yu, Chih Teng

AU - Liu, Su Ling

AU - Huang, Kuo Hsiung

AU - Chung, Kian Fan

AU - Kuo, Han Pin

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N2 - 1. Theophylline possesses anti-inflammatory activities in asthma. We examined whether theophylline and agents that modulate cyclic AMP can determine the survival and proliferation of progenitor cells. 2. Progenitor cells from the blood of normal and asthmatic subjects were cultured for 14 days in methylcellulose with GM-CSF, stem cell factor, IL-3 and IL-5. Apoptosis was measured by flow cytometry of propidium-iodide-stained cells. 3. A greater number of colonies with a higher proportion of cells of eosinophil lineage from asthmatics compared to normal subjects were grown. Theophylline (at 5 and 20 μg ml -1) significantly inhibited colony formation and increased apoptotic cells in asthmatics compared to control. Salbutamol (0.1, 1, 10 μM), dibutyryl-cAMP (0.1, 1 mM) and rolipram (0.1, 1 mM), a phosphodiesterase IV inhibitor, also dose-dependently decreased colony numbers and increased apoptosis of progenitor cells from asthmatics. 4. There was no significant effect of theophylline, db-cAMP, salbutamol or rolipram on colony formation or the survival of progenitor cells from normal subjects. AMP did not affect the colony formation and apoptosis. Expression of Bcl-2 protein on progenitor cells of asthma was downregulated by theophylline, salbutamol, db-cAMP and rolipram. 5. Theophylline and rolipram decreased colony formation committed to the eosinophil lineage, together with an increase in apoptosis through an inhibition of Bcl-2 expression effects that may occur through cAMP. The anti-inflammatory properties of theophylline include an inhibition of circulating progenitor cells.

AB - 1. Theophylline possesses anti-inflammatory activities in asthma. We examined whether theophylline and agents that modulate cyclic AMP can determine the survival and proliferation of progenitor cells. 2. Progenitor cells from the blood of normal and asthmatic subjects were cultured for 14 days in methylcellulose with GM-CSF, stem cell factor, IL-3 and IL-5. Apoptosis was measured by flow cytometry of propidium-iodide-stained cells. 3. A greater number of colonies with a higher proportion of cells of eosinophil lineage from asthmatics compared to normal subjects were grown. Theophylline (at 5 and 20 μg ml -1) significantly inhibited colony formation and increased apoptotic cells in asthmatics compared to control. Salbutamol (0.1, 1, 10 μM), dibutyryl-cAMP (0.1, 1 mM) and rolipram (0.1, 1 mM), a phosphodiesterase IV inhibitor, also dose-dependently decreased colony numbers and increased apoptosis of progenitor cells from asthmatics. 4. There was no significant effect of theophylline, db-cAMP, salbutamol or rolipram on colony formation or the survival of progenitor cells from normal subjects. AMP did not affect the colony formation and apoptosis. Expression of Bcl-2 protein on progenitor cells of asthma was downregulated by theophylline, salbutamol, db-cAMP and rolipram. 5. Theophylline and rolipram decreased colony formation committed to the eosinophil lineage, together with an increase in apoptosis through an inhibition of Bcl-2 expression effects that may occur through cAMP. The anti-inflammatory properties of theophylline include an inhibition of circulating progenitor cells.

KW - Apoptosis

KW - Asthma

KW - Bcl-2 protein

KW - CD34 + progenitor cells

KW - Phosphodiesterase inhibition

KW - Theophylline

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