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This Article Full Text Full Text (PDF) All Versions of this Article: 296/5/L839    most recent 90570.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Moretto, N. Articles by Patacchini, R. Search for Related Content PubMed PubMed Citation Articles by Moretto, N. Articles by Patacchini, R.

,β-Unsaturated aldehydes contained in cigarette smoke elicit IL-8 release in pulmonary cells through mitogen-activated protein kinases

¹Department of Pharmacology, Chiesi Farmaceutici, Parma, Italy; and ²Airway Pharmacology Group, School Of Translational Medicine, University Hospital Of South Manchester Foundation Trust Wythenshawe, Manchester, United Kingdom

Submitted 19 November 2008 ; accepted in final form 9 March 2009

Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease (COPD), a syndrome characterized by pulmonary neutrophil infiltration, chronic inflammation, and progressive tissue destruction. We examined here the acute effect of aqueous cigarette smoke extract (CSE) and of two ,β-unsaturated aldehydes (acrolein and crotonaldehyde) contained in CSE in cultured normal human lung fibroblasts and small airway epithelial cells. By examining a panel of 19 cytokines and chemokines, we found that IL-8 release was elevated by CSE as well as by acrolein, whereas other inflammatory mediators were mostly unaffected. CSE-evoked IL-8 release was mimicked by acrolein and crotonaldehyde at concentrations (3–60 µM each) found in CSE and fully prevented by 1 mM ,β-unsaturated aldehydes scavengers N-acetylcysteine (NAC) or sodium 2-mercaptoethanesulfonate. Neither the saturated aldehyde acetaldehyde nor H₂O₂ evoked IL-8 release. In addition, CSE or crotonaldehyde upregulated the release of IL-8 from alveolar macrophages from both COPD patients and healthy nonsmokers, indicating that this is a response common to cells involved in lung inflammation. CSE-evoked IL-8 release was accompanied by increased phosphorylation of p38 MAPK and ERK1/2. CSE-evoked p38 and ERK1/2 phosphorylation was mimicked by acrolein and inhibited by NAC. IL-8 release elicited by both acrolein and CSE was blocked by pharmacological inhibition of p38 and ERK1/2 phosphorylation. In summary, our data show that ,β-unsaturated aldehydes-evoked phosphorylation of p38 and ERK1/2 underlies IL-8 release elicited by CSE, thus shedding light on the mechanisms through which cigarette smoke can initiate inflammation in the lung.

epithelial cells; fibroblasts; chronic obstructive pulmonary disease; interleukin-8; p38; extracellular signal-regulated kinases 1 and 2; acrolein; crotonaldehyde

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