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Published on: July 10, 2018

Importance of p38 mitogen-activated protein kinase pathway in allergic airway remodelling and bronchial

Puneeta Nath1, Sum-Yee Leung, Alison Williams

  • 1National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK.

European Journal of Pharmacology
|July 18, 2006
PubMed

Insights

p38 mitogen-activated protein kinase (MAPK) inhibition reduces airway hyperresponsiveness and airway remodeling in a mouse asthma model. However, it does not impact eosinophilic inflammation or allergic responses.

Area of Science:

  • Immunology
  • Cell Biology
  • Respiratory Medicine

Background:

  • p38 mitogen-activated protein kinase (MAPK) is implicated in inflammatory cell activation and airway structural cell proliferation.
  • Chronic allergen exposure models are crucial for studying asthma pathogenesis and airway remodeling.
  • Selective inhibitors offer targeted therapeutic strategies for inflammatory diseases.

Purpose of the Study:

  • To investigate the role of p38 MAPK in a chronic asthma model.
  • To evaluate the efficacy of a selective p38 alpha and beta isoform inhibitor, SD282.
  • To determine the impact of p38 MAPK inhibition on bronchial hyperresponsiveness, inflammation, and airway remodeling.

Main Methods:

  • A chronic asthma model was established using 15 ovalbumin exposures in sensitized mice.
  • Two doses of the p38 MAPK inhibitor SD282 (30 and 90 mg/kg) were administered.
  • Key outcomes measured included bronchial hyperresponsiveness (PC200), bronchoalveolar lavage fluid (BALF) eosinophilia, airway smooth muscle area, goblet cell hyperplasia, and serum immunoglobulin E (IgE).
  • p38 MAPK activity was assessed via phosphorylated p38 expression using Western blots.

Main Results:

  • Allergen exposure induced bronchial hyperresponsiveness, eosinophilia, airway smooth muscle area increase, and goblet cell hyperplasia.
  • p38 MAPK activity was elevated post-allergen challenge and suppressed by SD282 at both doses.
  • SD282 treatment inhibited bronchial hyperresponsiveness and reduced airway smooth muscle and goblet cell hyperplasia.
  • SD282 did not affect eosinophil counts in BALF, serum IgE levels, or the overall allergic response.

Conclusions:

  • p38 MAPK plays a significant role in the pathogenesis of bronchial hyperresponsiveness.
  • Airway remodeling features, including smooth muscle and goblet cell hyperplasia, are regulated by p38 MAPK.
  • p38 MAPK inhibition is effective in mitigating bronchial hyperresponsiveness and airway remodeling, but not eosinophilic inflammation or allergic sensitization.
  • Chronic allergen-induced bronchial hyperresponsiveness may be linked to airway wall remodeling development.

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