Role of protease activated receptors type 2 (PAR2) during inflammation of airways and intestine

Funded Activity Summary

Epithelial cells lining the airways and the intestine contain receptors that are activated by proteases, which are protein cleaving enzymes. Activation of the subtype 2 of these receptors (PAR2) has been shown to cause salt and water transport in intestinal cells in culture. Little is known about the effects of PAR2-activation in the native airways and intestinal tissues. These tissues will be studied in the present project. A large increase in PAR2 is found in various diseases which are paralleled by a strong inflammation. Thus, PAR2 is likely to play a central role in intestinal diseases such as acute infectious diarrhea and chronic inflammatory bowel disease. PAR2 may also participate in the severe diarrhea frequently observed in patients with intestinal tumors. Similarly, inflammatory mediators released during airway infections are likely to act on PAR2, causing inappropriate secretion and a running nose. Most importantly, PAR2 are found in large excess in the airways of asthma patients. Since nothing is known about the impact of these receptors on fluid and electrolyte transport in the airways it appears timely and highly relevant to study the function of PAR2 in the airway epithelium. We will assess PAR2 mediated responses in human nasal biopsies. A more detailed analysis of the intracellular processes will be done in mouse trachea. We will further study the function of PAR2 in the intestinal epithelium. Activation of the ion transport via PAR2 will be examined in the mouse distal colon and in human rectal biopsies. We will utilize techniques such as Ussing chamber and patch clamp recordings to analyze the transport processes. The results should gain new inside into the role of PAR2 during inflammatory diseases of the airways and the intestine such as asthma and chronic inflammatory bowel diseases.

Funded Activity Details

Start Date: 01-01-2003

End Date: 01-01-2005

Funding Scheme: NHMRC Project Grants

Funding Amount: $235,500.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Medical biotechnology diagnostics (incl. biosensors)

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Airways | Bowel disease | Crohn's disease | Diarrhea | Electrolyte transport | Epithelium | Inflammation | Intestine | Protease activated receptors

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