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Cigarette smoke extract induced cytokine and chemokine gene expression changes in COPD macrophages

Kent, L, Smyth, LJC, Clayton, C, Scott, L, Cook, T, Stephens, R, Fox, S, Hext, P, Farrow, S and Singh, D 2008, 'Cigarette smoke extract induced cytokine and chemokine gene expression changes in COPD macrophages' , Cytokine, 42 (2) , pp. 205-216.

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Abstract

Macrophages are key inflammatory cells in chronic obstructive pulmonary disease (COPD). The transcriptional regulation of inflammatory signalling pathways by cigarette smoke (CS) in COPD macrophages is not well understood. We have studied the effects of acute CS exposure on COPD macrophage cytokine, chemokine and signal transduction gene expression profiles. Monocyte derived macrophages (MDMs) from whole blood from patients with COPD (n = 6) were stimulated with 1%, 10% and 25% CS extract (CSE) for 6 h for microarray and quantitative polymerase chain reaction (Q-PCR) analysis. We observed a CSE dose dependant increase in the numbers of significantly regulated genes; 24, 340 and 627 genes at 1%, 10% and 25% CSE, respectively. IL-8 mRNA levels were up-regulated by 10% CSE (2.25-fold increase, 95% CI 1.28–4.00). In contrast a range of other cytokines and chemokines were down-regulated at both 10% and 25% CSE, including IL-1β, -6, -10 and -18, chemokine ligands CCL-2, -3, -4, -5, -8, -15, -20 and CXCL-1, -2 and -10. Q-PCR and microarray data were highly correlated (r = 0.95, p = 0.0001). NF-κB component p50 and IκBα expression were suppressed by CSE, while there was up-regulation of the AP-1 components c-Jun, FOSL1 and FOSL2. Acute CSE exposure decreased macrophage inflammatory gene expression, with the exception of increased IL-8. There was diverse regulation of key inflammatory signal pathway genes. The effects of acute CS exposure appear to encompass both up-regulation of chemotaxis mechanisms through IL-8, but also down-regulation of innate immunity.

Item Type: Article
Themes: Subjects / Themes > Q Science > QR Microbiology
Subjects outside of the University Themes
Schools: Colleges and Schools > College of Science & Technology
Colleges and Schools > College of Science & Technology > School of Environment and Life Sciences
Journal or Publication Title: Cytokine
Publisher: Elsevier
Refereed: Yes
ISSN: 10434666
Depositing User: Users 29196 not found.
Date Deposited: 23 Dec 2010 13:56
Last Modified: 20 Aug 2013 17:44
URI: http://usir.salford.ac.uk/id/eprint/12682

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