RGD Reference Report - Different regulation of cigarette smoke induced inflammation in upper versus lower airways.

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Different regulation of cigarette smoke induced inflammation in upper versus lower airways.
Authors:	Huvenne, W Perez-Novo, CA Derycke, L De Ruyck, N Krysko, O Maes, T Pauwels, N Robays, L Bracke, KR Joos, G Brusselle, G Bachert, C
Citation:	Huvenne W, etal., Respir Res. 2010 Jul 23;11:100.
RGD ID:	4892029
Pubmed:	PMID:20650015 (View Abstract at PubMed)
PMCID:	PMC2915966 (View Article at PubMed Central)
DOI:	DOI:10.1186/1465-9921-11-100 (Journal Full-text)
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.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
CXCL6	Human	pneumonia		ISO	Cxcl5 (Mus musculus)	mRNA:increased expression:lung	RGD

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Genes (Homo sapiens)

CXCL6 (C-X-C motif chemokine ligand 6)

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Gene	Cxcl5	C-X-C motif chemokine ligand 5	Mus musculus
Gene	Cxcl6	C-X-C motif chemokine ligand 6	Rattus norvegicus

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