Welcome to !

Professor Geoffrey A Stewart*
Microbiology, School of Biomedical and Chemical Sciences
University of Western Australia
Perth, WA 6009
Email: geoffrey@cyllene.uwa.edu.au
Tel: +61-8-9346-3915
Fax: +61-8-9346-2912

Our interest in proteases stems from attempts to define the biological functions of allergens from the clinically important house dust mite, which is associated with respiratory diseases such as asthma. Together with colleagues, we identified and characterised several serine proteases and one cysteine protease. We have subsequently investigated how such biologically active allergens interact with the respiratory epithelium and whether such interactions might be pro-inflammatory. We showed that such allergens are indeed pro-inflammatory and, further, showed that these properties were mediated via interaction with protease activated receptors present on the epithelium, resulting in the release of cytokines such as IL-6 and IL-8 and prostanoids such as PGE2, as well as modulating tight junction protein structure (see Dr Clive Robinson). We also showed that the cysteine protease allergen (Der p 1) activated through PAR2 but inactivated PAR1, and have investigated the likely residues in the extracellular domain of the latter cleaved by the enzyme. We have also demonstrated that respiratory epithelium expressed all four members of the PAR family and that PAR2 expression is upregulated in diseases such as asthma. We have subsequently investigated the expression and pro-inflammatory function of PAR on prostate epithelial tissue as well as investigating the pro-inflammatory properties of a variety of proteases known to be associated with occupational asthma including papain and subtilisin.
Dr Clive Robinson, St George's Hospital Medical School, London, UK
Professor Philip Thompson, University of Western Australia, Perth, Australia
Dr Joel Pestel, Pasteur Institute, Lille, France
Dr Peter Henry, University of Western Australia, Perth, Australia
Stewart GA, Ward LD, Simpson RJ, Thompson PJ. The group III allergen from the house dust mite Dermatophagoides pteronyssinus is a trypsin-like enzyme. Immunology 1992; 75:29-35.

King C, Brennan S, Thompson PJ, Stewart GA. Dust mite proteolytic allergens induce cytokine release from cultured airway epithelium. J Immunol 1998; 161:3645-51.

Knight DA, Lim S, Scaffidi AK, Roche N, Chung KF, Stewart GA, Thompson PJ. Protease-activated receptors in human airways: upregulation of PAR-2 in respiratory epithelium from patients with asthma. J Allergy Clin Immunol 2001; 108:797-803.

Asokananthan N, Graham PT, Stewart DJ, Bakker AJ, Eidne KA, Thompson PJ, Stewart GA. House dust mite allergens induce proinflammatory cytokines from respiratory epithelial cells: The cysteine protease allergen, Der p 1, activates protease-activated receptor (PAR)-2 and inactivates PAR-1. J Immunol 2002; 169:4572-8.

Asokananthan N, Graham PT, Fink J, Knight DA, Bakker AJ, McWilliam AS, Thompson PJ, Stewart GA. Activation of protease-activated receptor (PAR)-1, PAR-2, and PAR-4 stimulates IL-6, IL-8, and prostaglandin E2 release from human respiratory epithelial cells. J Immunol 2002; 168:3577-85.

Questions/suggestions? Please contact the Network Administrator.
Copyright © by International Protease Network All Right Reserved.