Factors modulating TLR2, TLR4 and HBD2 expression in respiratory epithelium in COPD
Citation:
Ruth MacRedmond, 'Factors modulating TLR2, TLR4 and HBD2 expression in respiratory epithelium in COPD', [thesis], Trinity College (Dublin, Ireland). School of Medicine. Discipline of Clinical Medicine, 2006, pp 228Download Item:
Abstract:
The innate immune response of the respiratory epithelium, employing mechanisms of germ-line encoded, genetically conserved pattern recognition to “non-self’ organisms, is an important component of host defence against inhaled pathogens. Key components of innate immunity include the toll-like receptors, including TLR4 that signals the response to Gram-negative elements and TLR2 signalling Gram-positive patterns, and antimicrobial peptides such as human beta- defensin 2. Airway infection is important in COPD, and this project explores elements of innate immunity pertinent to COPD. The respiratory epithelial cell line A549 and the renal epithelial cell line, HEK 293 (which are unresponsive to LPS) were used as a model system. Gene expression was determined by semi-quantitative rtPCR, Real Time PCR and by promoter-linked luciferase activity. Western blotting, immunohistochemistry, laser scanning cytometry and ELISA determined protein expression. The role of specific components of signalling pathways was further explored by transfection of functionally active or inactive transgene constructs. Human respiratory epithelial cells in vivo were harvested by brushing of nasal and tracheo-bronchial epithelium.
In the first part of this study, I provide evidence for a critical role for TLR4 in LPS-induced HBD2 expression in airway epithelial cells. Transcriptional regulation of HBD2 is further elucidated with demonstration of the role of the adaptor proteins MyD88 and Mai in this reaction.
Author: MacRedmond, Ruth
Advisor:
O'Neill, ShaneGreene, Catherine
Qualification name:
Doctor of Medicine (M.D.)Publisher:
Trinity College (Dublin, Ireland). School of Medicine. Discipline of Clinical MedicineNote:
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