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Gastrin-releasing peptide blockade as a broad-spectrum anti-inflammatory therapy for asthma

Shutang Zhou1, Erin N Potts, Frank Cuttitta

  • 1Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA. shutang.zhou@duke.edu

Proceedings of the National Academy of Sciences of the United States of America
|January 22, 2011
PubMed

Insights

Gastrin-releasing peptide (GRP) blockade effectively reduced airway hyperreactivity and inflammation in mouse models of asthma. This suggests GRP blockade is a promising therapeutic strategy for preventing and treating asthma.

Area of Science:

  • Pulmonary Medicine
  • Immunology
  • Pharmacology

Background:

  • Asthma affects over 300 million people globally, with early mechanisms remaining unclear.
  • Infants with bronchopulmonary dysplasia (BPD) often develop asthma, a condition linked to pulmonary neuroendocrine cells producing gastrin-releasing peptide (GRP).

Purpose of the Study:

  • To investigate the role of GRP in mediating asthma and airway inflammation.
  • To evaluate the therapeutic potential of GRP blockade in asthma models.

Main Methods:

  • Two murine asthma models were used: ozone exposure for air pollution-induced airway hyperreactivity (AHR) and ovalbumin (OVA)-induced allergic airway disease.
  • Mice were treated with a GRP blocking agent (77427) or antibody (2A11) prior to ozone or OVA challenge.
  • Effects on AHR, bronchoalveolar lavage (BAL) cell counts, and BAL cytokines were assessed. GRP receptor (GRPR) phosphorylation was also examined.

Main Results:

  • GRP blockade significantly abrogated AHR, reduced BAL macrophages and granulocytes, and decreased key asthma-related cytokines (Th1, Th2, Th17, macrophage, and neutrophil-derived).
  • Dexamethasone showed less pronounced effects compared to GRP blockade.
  • GRP blockade inhibited GRPR serine phosphorylation in response to ozone or OVA challenge.

Conclusions:

  • Gastrin-releasing peptide plays a mediating role in airway hyperreactivity and inflammation in mouse asthma models.
  • GRP blockade demonstrates potential as a broad-spectrum therapeutic for preventing and treating human asthma.

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