Airway hyperresponsiveness (AHR) is a cardinal feature of asthma that is aggravated by environmental air pollution (EAP). Splenocyte tyrosine kinase Syk has been associated with asthma pathogenesis. Therefore, we sought to investigate the effect of Syk inhibition on AHR and its exacerbation by EAP. For this purpose, we examined Syk protein expression in lung homogenates from three murine models of ovalbumin (OVA)-induced asthma expressing different pathophysiological features of the disease: airway inflammation, AHR and remodeling. Increased Syk expression was observed only in the chronic model of airway inflammation and remodeling. In vivo Syk inhibition attenuates AHR in this model, and further augmentation induced by EAP without affecting the underlying airway inflammation. We demonstrated, for the first time, that Syk inhibition effectively reverted AHR in an already established chronic model of asthma. These findings highlight the therapeutic potential of targeting Syk for the treatment of asthma and its exacerbations by EAP.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/33357 |
| Date | 21 November 2012 |
| Creators | Castellanos Penton, Patricia |
| Contributors | Chow, Chung-Wai, Scott, Jeremy A. |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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