Dr N Asokananthan Microbiology, School of Biomedical and Chemical Sciences University of Western Australia Perth, Western Australia 6009 Email: asok@cyllene.uwa.edu.au Tel: +61-8-9346-2514 Fax: +61-8-9346-2912 Homepage: Research Our interest in proteases stems from attempts to investigate how 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. 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 and fetal lung fibroblasts expressed all four members of the PAR family and that PAR2 expression is up regulated in diseases such as asthma in the respiratory epithelium. We have subsequently investigated the expression and pro-inflammatory function of PAR on prostate epithelial tissue. Our current interest is also in understanding the signal transduction pathway associated with protease and peptide-dependant receptor activation. Collaborations Professor Philip Thompson, University of Western Australia, Perth, Australia Dr Karin Eidne, University of Western Australia, Perth, Australia Dr Tony Bakker, University of Western Australia, Perth, Australia Professor Howard Mitchell, University of Western Australia, Perth, Australia Publications Knight DA, Asokananthan N, Watkins DN, Misso NL, Thompson PJ, Stewart GA. Oncostatin M synergises with house dust mite proteases to induce the production of PGE(2) from cultured lung epithelial cells. Br J Pharmacol. 2000; 131:465-72. 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.