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Title: The effects of cigarette smoke extract on inflammatory responses in COPD airway epithelial cells
Author: Comer , David Michael
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2013
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For in vitro studies of airway pathophysiology, primary epithelial cells have many advantages over immortalised cell lines. Nasal epithelial cells (PNECs) are easier to obtain than bronchial epithelial cells (PBECs) and are used as an alternative model. My initial objective was to compare PNECs and PBECs from subjects with COPD to establish if these cells respond similarly to pro-inflammatory stimuli. Furthermore, I hypothesised that airway epithelial cells from subjects with COPD respond differently to Pseudomonas aeruginosa lipopolysaccharide (PA LPS) after cigarette smoke extract (CSE) exposure than cells obtained from healthy smokers without airflow obstruction (HS) and also from cells from non-smokers (NS). Cell cultures from paired nasal and bronchial brushings from 21 COPD subjects were incubated with CSE prior to stimulation with PA LPS. IL-S release correlated significantly between the two cell types. LL-6 secretion was significantly less from PBECs compared to PNECs and secreted concentrations did not correlate. Four h CSE incubation was immunosuppressive for both PNECs and PBECs, however prolonged incubation (24 h) was proinflammatory solely for PNECs. CSE reduced TLR-4 expression in PBECs only after 24 h, but was without effect on mRNA expression. PBECs from 16 COPD subjects, 10 HS and 11 NS were cultured at air-liquid interface. Cultures were incubated with CSE prior to stimulation with PA LPS. Constitutive release of IL-S and IL-6 was greatest from the COPD cultures. However, CSE pre-treatment followed by PA LPS stimulation reduced lL-8 release from COPD PBECs, but increased it from HS and NS cultures. TLR-4 expression, CSE treatment reduced MAPK and NF• KB activation in COPD cultures but not in the HS or NS groups. In subjects with COPD, PNECs cannot substitute for PBECs in airway inflammation studies. CSE attenuates inflammatory responses to PA LPS in cells from people with COPD but not those from HS and NS.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available