Cystic fibrosis (CF) female patients have a worse prognosis compared to their male counterparts. CF patients infected with Pseudomonas aeruginosa have also been shown to have dysregulated cytokine profiles. Therefore, we studied the importance of sex and interleukin-10 in the susceptibility of C57BL/6 mice to pulmonary infection with P. aeruginosa. The results clearly demonstrate that both wildtype and interleukin-10 knockout (KO) female mice are more susceptible to P. aeruginosa infection than males, and that they mount a stronger inflammatory response in the lungs. / Several animal models of CF show most of the CF symptoms; however, only a few of these display the CF lung phenotype. The cystic fibrosis transmembrane conductance regulator (Cftr)-KO mice that we developed in collaboration with Drs. Tsui and Kent represent a unique model of spontaneously occurring lung disease. We studied the characteristics of this model and analyzed the differences between the lungs of wildtype and Cftr-KO mice by assessing their histopathological status, gene and protein expression and fatty acid profiles. / We recently developed a novel non-invasive method of lung infection. The studies described contain major improvements for lung infection techniques employing P. aeruginosa bacteria embedded in agar beads. This novel and less invasive technique is crucially important in studying the host response to bacterial infection using the Cftr-KO mouse model. / CF lung disease is also characterized by imbalanced lipid profiles. Interestingly, docosahexanoic acid (DHA) has been shown to have antiinflammatory properties and to reverse intestinal and pancreatic pathologies in a CF mouse model. We have therefore treated our Cftr-KO mice developing spontaneous lung disease with DHA and observed a reduction in lung inflammation in the CF-affected organs compared to the untreated Cftr-KO mice. / It has also been demonstrated that ceramide is crucially important for P. aeruginosa internalization. Fenretinide is a synthetic retinoid inducing the cellular level of ceramide. Using our Cftr-KO mouse model, we tested the effect of fenretinide treatment during the course of lung infection with P. aeruginosa. Interestingly, we observed major decrease in the bacterial burden of Cftr-KO mice that were treated with fenretinide.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.100615 |
| Date | January 2005 |
| Creators | Guilbault, Claudine. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Division of Experimental Medicine.) |
| Rights | © Claudine Guilbault, 2005 |
| Relation | alephsysno: 002329582, proquestno: AAINR25161, Theses scanned by UMI/ProQuest. |
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