Comparison of Nasal and Bronchial Epithelial Cells Obtained from Patients with COPD

Abstract

For in vitro studies of airway pathophysiology, primary epithelial cells have many advantages over immortalised cell lines. Nasal epithelial cells are easier to obtain than bronchial epithelial cells and can be used as an alternative for in vitro studies. Our objective was to compare nasal and bronchial epithelial cells from subjects with COPD to establish if these cells respond similarly to pro-inflammatory stimuli. Cell cultures from paired nasal and bronchial brushings (21 subjects) were incubated with cigarette smoke extract (CSE) prior to stimulation with Pseudomonas aeruginosa lipopolysaccharide. IL-6 and IL-8 were measured by ELISA and Toll-like receptor 4 (TLR-4) message and expression by RT-PCR and FACS respectively. IL-8 release correlated significantly between the two cell types. IL-6 secretion was significantly less from bronchial compared to nasal epithelial cells and secreted concentrations did not correlate. A 4 h CSE incubation was immunosuppressive for both nasal and bronchial cells, however prolonged incubation for 24 h was pro-inflammatory solely for the nasal cells. CSE reduced TLR-4 expression in bronchial cells only after 24 h, and was without effect on mRNA expression. In subjects with COPD, nasal epithelial cells cannot substitute for in vitro bronchial epithelial cells in airway inflammation studies.

The expression of the eotaxins IL-6 and CXCL8 in human epithelial cells from various levels of the respiratory tract

“…Looking at the absolute values in the controls in our study, the bronchial epithelial cells produced the smallest amounts of IL-6 protein. This is consistent with previously published results [26,34]. Stimulation with TNF-α resulted in a greater increase in the IL-6 level in bronchial cells.…”

“…In general, the reactivity of the nasal, bronchial and small airway epithelial cells was qualitatively similar, although in some cases substantial differences were observed. Similar differences in the reactivity of paired cultures of human nasal and bronchial epithelial cells were also observed by other authors [26,29]. We confirmed the earlier observations of many authors that CCL26 was the main eotaxin detected in cultures of human bronchial epithelial cells stimulated with IL-4 or IL-13 [30,31].…”

“…The highest changes in IL-6 expression were noted in bronchial cells, but only after mediator stimulation. This is contrary to the results of Comer et al, who showed a higher IL-6 protein production in a nasal epithelial cell culture and even a lack of IL-6 production by bronchial epithelial cells after LPS stimulation [26]. This apparent discrepancy between the studies could be due to the different models of data presentation.…”

“…Experiments with cultures of paired undifferentiated nasal and bronchial epithelial cells obtained from patients suffering from various respiratory disorders showed differences in the production of IL-6, CXCL8 and numerous mediators of inflammation in response to TNF-α and IL-1β [25]. Comer et al showed that nasal epithelial cells obtained from COPD subjects could not be used as a substitute for bronchial epithelial cells for in vitro studies due to the substantially different IL-6 release [26]. Also, nasal and bronchial epithelial cells from children with or without asthma behaved differently under basal conditions and after IL-13 stimulation [27].…”

Airway epithelial cell apoptosis and inflammation in COPD, smokers and nonsmokers

“…However, the weight of evidence would support that CSE has predominantly pro-inflammatory [2,15,16] as opposed to immunosuppressive effects [17,18] on bronchial epithelial cells. Although there is evidence that nasal epithelial cells can act as a satisfactory substitute for bronchial epithelial cells for certain end-points, we have recently shown that bronchial epithelial cells respond differently to nasal epithelial cells to CSE treatment [19].…”