Cigarette smoke induces IL-8, but inhibits eotaxin and RANTES release from airway smooth muscle.
BACKGROUND
Cigarette smoke is the leading risk factor for the development of chronic obstructive pulmonary disease (COPD) an inflammatory condition characterised by neutrophilic inflammation and release of proinflammatory mediators such as interleukin-8 (IL-8). Human airway smooth muscle cells (HASMC) are a source of proinflammatory cytokines and chemokines. We investigated whether cigarette smoke could directly induce the release of chemokines from HASMC.


METHODS
HASMC in primary culture were exposed to cigarette smoke extract (CSE) with or without TNFalpha. Chemokines were measured by enzyme-linked immunosorbent assay (ELISA) and gene expression by real time polymerase chain reaction (PCR). Data were analysed using one-way analysis of variance (ANOVA) followed by Bonferroni's t test


RESULTS
CSE (5, 10 and 15%) induced IL-8 release and expression without effect on eotaxin or RANTES release. At 20%, there was less IL-8 release. TNFalpha enhanced CSE-induced IL-8 release and expression. However, CSE (5-30%) inhibited TNFalpha-induced eotaxin and RANTES production. The effects of CSE on IL-8 release were inhibited by glutathione (GSH) and associated with the induction of the oxidant sensing protein, heme oxygenase-1.


CONCLUSIONS
Cigarette smoke may directly cause the release of IL-8 from HASMC, an effect enhanced by TNF-alpha which is overexpressed in COPD. Inhibition of eotaxin and RANTES by cigarette smoke is consistent with the predominant neutrophilic but not eosinophilic inflammation found in COPD.
Oltmanns
Ute
U
Experimental Studies National Heart & Lung Institute, Imperial College, London SW36LY, UK. u.oltmanns@imperial.ac.uk
Chung
Kian F
KF
Walters
Matthew
M
John
Matthias
M
Mitchell
Jane A
JA
D002478:Cells, Cultured; D054413:Chemokine CCL11; D018946:Chemokine CCL5 / Q000378:metabolism*; D019742:Chemokines, CC / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D013638:Tars / Q000494:pharmacology*
C515456:CCL11 protein, human; D054413:Chemokine CCL11; D018946:Chemokine CCL5; D019742:Chemokines, CC; D016209:Interleukin-8; D013638:Tars; C024746:tobacco tar