Endogenous nitric oxide downregulates the Bcl-2 expression of eosinophils through mitogen-activated protein kinase in bronchial asthma

Suh Hwa Maa, Chun Hua Wang, Chien Ying Liu, Horng Chyuan Lin, Kuo Hsiung Huang, Han Pin Kuo

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background: Eosinophil apoptosis might play a crucial role in the maintenance of persistent airway inflammation in asthma. Nitric oxide (NO) synthase activity is upregulated in eosinophils of asthmatic patients. Mitogen-activated protein kinase (MAPK) is implicated in regulating eosinophil apoptosis by modulating Bcl-2 expression. NO-induced cell apoptosis is associated with an inhibition of Bcl-2 expression. Objective: We sought to study whether NO might induce eosinophil apoptosis through extracellular signal-regulated protein kinase (ERK) or p38 MAPK pathways and Bcl-2 expression. Methods: Eosinophils were freshly isolated from peripheral blood of 16 asthmatic patients and 12 healthy subjects and then cultured with or without the NO synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) at 1 and 10 mmol/L for 16 hours. The expression of Bcl-2 and induced NO synthase on eosinophils was analyzed by means of flow cytometry. Apoptosis was assessed by means of propidium iodide and DNA ladder. The activity of ERK and p38 MAPK was determined by means of Western blotting. Results: The induced NO synthase immunoreactivities and the spontaneous release of nitrite from the eosinophils of asthmatic patients were higher compared with those of healthy subjects. Eosinophils of asthmatic patients were found to express more highly constitutive Bcl-2 than those of healthy subjects. After incubation for 16 hours, the expression of Bcl-2 on eosinophils from patients with asthma was significantly enhanced by L-NAME. The percentage of apoptosis was decreased by the addition of 1 mmol/L L-NAME in patients with asthma. The activity of p38 MAPK and ERK in eosinophils from patients with asthma was enhanced in the presence of L-NAME. An inhibition of MAPK reduced the Bcl-2 expression and increased eosinophil apoptosis in patients with asthma. Conclusion: We concluded that inhibition of endogenous NO might increase the expression of Bcl-2 in eosinophils from patients with asthma through the signaling pathway of ERK or p38 MAPK, which in turn decrease the apoptosis.

Original languageEnglish
Pages (from-to)761-767
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume112
Issue number4
DOIs
Publication statusPublished - Oct 1 2003
Externally publishedYes

Fingerprint

Mitogen-Activated Protein Kinases
Eosinophils
Nitric Oxide
Down-Regulation
Asthma
Apoptosis
NG-Nitroarginine Methyl Ester
p38 Mitogen-Activated Protein Kinases
Nitric Oxide Synthase
Healthy Volunteers
MAP Kinase Signaling System
Propidium
Extracellular Signal-Regulated MAP Kinases
Nitrites
Protein Kinases
Flow Cytometry
Western Blotting
Maintenance
Inflammation

Keywords

  • Apoptosis
  • Bcl-2 protein
  • Eosinophils
  • Mitogen-activated protein kinase
  • Nitric oxide

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Endogenous nitric oxide downregulates the Bcl-2 expression of eosinophils through mitogen-activated protein kinase in bronchial asthma. / Maa, Suh Hwa; Wang, Chun Hua; Liu, Chien Ying; Lin, Horng Chyuan; Huang, Kuo Hsiung; Kuo, Han Pin.

In: Journal of Allergy and Clinical Immunology, Vol. 112, No. 4, 01.10.2003, p. 761-767.

Research output: Contribution to journalArticle

Maa, Suh Hwa ; Wang, Chun Hua ; Liu, Chien Ying ; Lin, Horng Chyuan ; Huang, Kuo Hsiung ; Kuo, Han Pin. / Endogenous nitric oxide downregulates the Bcl-2 expression of eosinophils through mitogen-activated protein kinase in bronchial asthma. In: Journal of Allergy and Clinical Immunology. 2003 ; Vol. 112, No. 4. pp. 761-767.
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AU - Lin, Horng Chyuan

AU - Huang, Kuo Hsiung

AU - Kuo, Han Pin

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AB - Background: Eosinophil apoptosis might play a crucial role in the maintenance of persistent airway inflammation in asthma. Nitric oxide (NO) synthase activity is upregulated in eosinophils of asthmatic patients. Mitogen-activated protein kinase (MAPK) is implicated in regulating eosinophil apoptosis by modulating Bcl-2 expression. NO-induced cell apoptosis is associated with an inhibition of Bcl-2 expression. Objective: We sought to study whether NO might induce eosinophil apoptosis through extracellular signal-regulated protein kinase (ERK) or p38 MAPK pathways and Bcl-2 expression. Methods: Eosinophils were freshly isolated from peripheral blood of 16 asthmatic patients and 12 healthy subjects and then cultured with or without the NO synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) at 1 and 10 mmol/L for 16 hours. The expression of Bcl-2 and induced NO synthase on eosinophils was analyzed by means of flow cytometry. Apoptosis was assessed by means of propidium iodide and DNA ladder. The activity of ERK and p38 MAPK was determined by means of Western blotting. Results: The induced NO synthase immunoreactivities and the spontaneous release of nitrite from the eosinophils of asthmatic patients were higher compared with those of healthy subjects. Eosinophils of asthmatic patients were found to express more highly constitutive Bcl-2 than those of healthy subjects. After incubation for 16 hours, the expression of Bcl-2 on eosinophils from patients with asthma was significantly enhanced by L-NAME. The percentage of apoptosis was decreased by the addition of 1 mmol/L L-NAME in patients with asthma. The activity of p38 MAPK and ERK in eosinophils from patients with asthma was enhanced in the presence of L-NAME. An inhibition of MAPK reduced the Bcl-2 expression and increased eosinophil apoptosis in patients with asthma. Conclusion: We concluded that inhibition of endogenous NO might increase the expression of Bcl-2 in eosinophils from patients with asthma through the signaling pathway of ERK or p38 MAPK, which in turn decrease the apoptosis.

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