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Related Experiment Videos

Tryptase mediates hyperresponsiveness in isolated guinea pig bronchi

V E Barrios1, S C Middleton, M A Kashem

  • 1Department of Pharmacology, Amgen, Inc., Thousand Oaks, CA 91320, USA.

Life Sciences
|January 7, 1999
PubMed
Summary

Secretory leukocyte protease inhibitor (SLPI) reduces airway hyperresponsiveness by inhibiting tryptase, a key asthma mediator. This suggests SLPI holds therapeutic potential for asthma treatment.

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Area of Science:

  • Pulmonary Medicine
  • Allergy and Immunology
  • Biochemistry

Background:

  • Airway hyperresponsiveness is central to asthma pathophysiology.
  • Tryptase, released by mast cells, is implicated in inducing airway hyperresponsiveness.
  • Tryptase inhibitors are being investigated as potential asthma therapeutics.

Purpose of the Study:

  • To evaluate the therapeutic potential of Secretory leukocyte protease inhibitor (SLPI) in asthma.
  • To assess SLPI's anti-tryptase activity and its effects on airway hyperresponsiveness.
  • To compare SLPI's efficacy with a small molecule tryptase inhibitor, APC-366.

Main Methods:

  • In vitro and ex vivo models of airway hyperresponsiveness were utilized.
  • The effects of SLPI on tryptase-mediated hyperresponsiveness were measured.

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  • Airway smooth muscle from antigen-sensitized animals was exposed to antigen.

    • Main Results:

    • SLPI demonstrated significant inhibition of tryptase-mediated airway hyperresponsiveness in vitro.
    • SLPI attenuated airway hyperresponsiveness in ex vivo models involving antigen exposure.
    • The small molecule tryptase inhibitor APC-366 exhibited comparable inhibitory effects.

    Conclusions:

    • Tryptase plays a significant role in the development of airway hyperresponsiveness.
    • SLPI effectively inhibits tryptase activity and reduces airway hyperresponsiveness.
    • SLPI shows promise as a potential therapeutic agent for managing asthma.