[Truncated] Respiratory tract infections caused by influenza A viruses are associated with considerable morbidity and mortality throughout the world. Furthermore, influenza A viral infections can exacerbate pre-existing asthma and induce several hallmark features of the condition, including airways inflammation and airways hyperresponsiveness i:n otherwise healthy individuals. As a result, murine models of influenza A infection are a valuable and frequently used platform for examining potential modulators of respiratory tract inflammatory processes, such as protease-activated receptors (PARs). PARs are 7- transmembrane domain, G-protein coupled receptors that act as sensors of extracellular proteolytic activity. PAR activation typically involves the cleavage of a specific site within the extracellular N-terminal region of the receptor, which generates a newly formed tethered ligand sequence that interacts with the 2nd extracellular loop of the receptor to confer cellular signalling. Activation of a particular PAR isoform, P AR2, has previously been shown to be beneficial in various models of inflammatory airway disease, although the effect of P AR2 activation in virus-induced models of airways inflammation has not been determined. Thus, this thesis set out to examine the effect of P AR2 activators on inflammatory events within a murine model of influenza A virusinduced airways inflammation.
|Qualification||Doctor of Philosophy|
|Publication status||Unpublished - 2007|