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Aerosolized Syk antisense suppresses Syk expression, mediator release from macrophages, and pulmonary inflammation

G R Stenton1, M K Kim, O Nohara

  • 1Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.

Journal of Immunology (Baltimore, Md. : 1950)
|March 22, 2000
PubMed

Insights

Aerosolized Syk antisense oligodeoxynucleotides (ASO) reduced Syk protein tyrosine kinase (PTK) expression in rat lungs. Syk ASO treatment suppressed inflammatory mediator release and pulmonary inflammation, indicating potential asthma therapy.

Area of Science:

  • Immunology
  • Molecular Biology
  • Pharmacology

Background:

  • Syk protein tyrosine kinase (PTK) is crucial for signaling in leukocytes, particularly in macrophages.
  • Fcgamma-receptor activation in macrophages triggers Syk PTK phosphorylation and downstream events like phagocytosis and mediator release.

Purpose of the Study:

  • To investigate the efficacy of aerosolized Syk antisense oligodeoxynucleotides (ASO) in reducing Syk PTK expression and Syk-dependent pulmonary inflammation in vivo.
  • To assess the impact of Syk ASO on mediator release from alveolar macrophages.

Main Methods:

  • Administration of Syk ASO via aerosol to rat lungs.
  • Quantitative reverse transcription PCR (RT-PCR) and RT-in situ PCR to measure Syk mRNA expression.
  • Western blot analysis to confirm Syk PTK protein expression levels.
  • Stimulation of alveolar macrophages with IgG-anti-IgG complexes to assess mediator release (nitric oxide, TNF, IL-1beta).
  • Evaluation of antigen-induced pulmonary inflammation.

Main Results:

  • Aerosolized Syk ASO significantly reduced Syk mRNA and protein tyrosine kinase expression in rat alveolar macrophages.
  • Syk ASO treatment suppressed Fcgamma-receptor-mediated nitric oxide and TNF production by alveolar macrophages.
  • Fcgamma-receptor-induced IL-1beta release remained unaffected by Syk ASO treatment.
  • Syk ASO administration effectively suppressed antigen-induced pulmonary inflammation.

Conclusions:

  • Aerosolized Syk ASO is effective in reducing Syk PTK expression and associated inflammatory responses in the lungs.
  • Syk ASO demonstrates potential as an anti-inflammatory therapeutic agent for respiratory disorders like asthma.

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