Abstract
BackgroundCigarette smoke (CS) is known to initiate a cascade of mediator release and accumulation of immune and inflammatory cells in the lower airways. We investigated and compared the effects of CS on upper and lower airways, in a mouse model of subacute and chronic CS exposure.MethodsC57BL/6 mice were whole-body exposed to mainstream CS or air, for 2, 4 and 24 weeks. Bronchoalveolar lavage fluid (BAL) was obtained and tissue cryosections from nasal turbinates were stained for neutrophils and T cells. Furthermore, we evaluated GCP-2, KC, MCP-1, MIP-3α, RORc, IL-17, FoxP3, and TGF-β1 in nasal turbinates and lungs by RT-PCR.ResultsIn both upper and lower airways, subacute CS-exposure induced the expression of GCP-2, MCP-1, MIP-3α and resulted in a neutrophilic influx. However, after chronic CS-exposure, there was a significant downregulation of inflammation in the upper airways, while on the contrary, lower airway inflammation remained present. Whereas nasal FoxP3 mRNA levels already increased after 2 weeks, lung FoxP3 mRNA increased only after 4 weeks, suggesting that mechanisms to suppress inflammation occur earlier and are more efficient in nose than in lungs.ConclusionsAltogether, these data demonstrate that CS induced inflammation may be differently regulated in the upper versus lower airways in mice. Furthermore, these data may help to identify new therapeutic targets in this disease model.
Highlights
Cigarette smoke (CS) is known to initiate a cascade of mediator release and accumulation of immune and inflammatory cells in the lower airways
The role of lymphocytes in the development of Chronic Obstructive Pulmonary Disease (COPD) is demonstrated by the fact that chronic cigarette smoke (CS) exposure leads to an increase in peribronchial lymphoid follicles in both mice and humans [8,9], the importance of these lymphoid follicles remains unclear [10]
Bronchoalveolar lavage fluid (BAL) fluid analysis 2-wk, 4-wk and 24-wk CS exposure caused a significant increase in the absolute numbers of total cells, lymphocytes and neutrophils in the BAL fluid
Summary
Cigarette smoke (CS) is known to initiate a cascade of mediator release and accumulation of immune and inflammatory cells in the lower airways. Epidemiological data suggest that 75% of the COPD patients have concomitant nasal symptoms and more than 1/3 of patients with sinusitis have lower airway symptoms of asthma or COPD [2]. These arguments stress the significant sinonasal inflammation in patients with lower airway complaints, beyond the scope of allergic inflammation [3,4,5]. The role of lymphocytes in the development of COPD is demonstrated by the fact that chronic cigarette smoke (CS) exposure leads to an increase in peribronchial lymphoid follicles in both mice and humans [8,9], the importance of these lymphoid follicles remains unclear [10]
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