Different regulation of cigarette smoke induced inflammation in upper versus lower airways.
BACKGROUND
Cigarette 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.


METHODS
C57BL/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-3alpha, RORc, IL-17, FoxP3, and TGF-beta1 in nasal turbinates and lungs by RT-PCR.


RESULTS
In both upper and lower airways, subacute CS-exposure induced the expression of GCP-2, MCP-1, MIP-3alpha 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.


CONCLUSIONS
Altogether, 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.
Huvenne
Wouter
W
Upper Airways Research Laboratory, ENT Department, Ghent University Hospital, Ghent University, Belgium. Wouter.Huvenne@UGent.be
Pérez-Novo
Claudina A
CA
Derycke
Lara
L
De Ruyck
Natalie
N
Krysko
Olga
O
Maes
Tania
T
Pauwels
Nele
N
Robays
Lander
L
Bracke
Ken R
KR
Joos
Guy
G
Brusselle
Guy
G
Bachert
Claus
C
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009297:Nasal Mucosa / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D009666:Nose / Q000276:immunology*; D011014:Pneumonia / Q000235:genetics / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects*; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014420:Turbinates / Q000276:immunology
D018836:Inflammation Mediators; D012333:RNA, Messenger