Proteinase-activated receptor 2 activation in the airways enhances antigen-mediated airway inflammation and airway hyperresponsiveness through different pathways.

Abstract

BACKGROUND:

Serine proteinases such as mast cell tryptase, trypsin-like enzymes, and certain allergens are important in the pathogenesis of asthma. These proteinases can activate the proteinase-activated receptor (PAR)-2, which has been shown to be upregulated in the airways of patients with asthma.

OBJECTIVE:

The purpose of this study was to investigate PAR-2 activation in the airways during allergen challenge and its effects on the 2 principle features of asthma, airway inflammation and airway hyperresponsiveness (AHR).

METHODS:

Proteinase-activated receptor 2 activating peptide SLIGRL-NH2 (PAR-2 activating peptide [ap]) or control peptide LSIGRL-NH2 (PAR-2 control peptide [cp]) was administered alone or in conjunction with ovalbumin intranasally to mice, and AHR and airway inflammation were evaluated.

RESULTS:

PAR2ap did not induce AHR or airway inflammation in ovalbumin-sensitized mice that had not been challenged with ovalbumin. When administered with ovalbumin, PAR-2ap enhanced AHR and airway inflammation compared with ovalbumin administered alone or with PAR-2cp. The enhanced AHR persisted for 5 days, whereas the enhancement to airway inflammation dissipated. Mice administered PAR-2ap alone during the 5 days after the final antigen challenge demonstrated an additional enhancement to airway inflammation compared with the control animals. PAR-2ap administered with allergen increased TNF and IL-5 mRNA in lung tissue and IL-13 and TNF in bronchoalveolar lavage fluid.

CONCLUSION:

Exogenous PAR-2 activation in parallel with allergen challenge enhances allergen-mediated AHR and airway inflammation through distinct mechanisms. PAR-2 activation can also enhance established airway inflammation even when dissociated from exposure to allergen. Therefore, PAR-2 activation may play a pathogenic role in the development of AHR and airway inflammation.

• Authors: Cory Ebeling, Paul Forsythe, Jason Ng, John R Gordon, Morley Hollenberg, Harissios Vliagoftis
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 115 Issue 3 Pg. 623-30 (Mar 2005) ISSN: 0091-6749 [Print] United States
• PMID: 15753914 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-13
• Interleukin-5
• Oligopeptides
• RNA, Messenger
• Receptors, Proteinase-Activated
• Tumor Necrosis Factor-alpha
• Ovalbumin

Topics

• Animals
• Bronchoalveolar Lavage Fluid (immunology)
• Immunohistochemistry
• Inflammation (immunology)
• Interleukin-13 (immunology)
• Interleukin-5 (immunology)
• Lung (drug effects, immunology, metabolism)
• Male
• Mice
• Oligopeptides (pharmacology)
• Ovalbumin (immunology)
• RNA, Messenger (analysis)
• Receptors, Proteinase-Activated (immunology, metabolism)
• Respiratory Hypersensitivity (immunology)
• Tumor Necrosis Factor-alpha (drug effects, immunology)