Nicotine and oxidative cigarette smoke constituents induce immune-modulatory and pro-inflammatory dendritic cell responses

Robert Vassallo, Paula R. Kroening, Joseph Parambil, Hirohito Kita

Research output: Contribution to journalArticle

76 Scopus citations

Abstract

Chronic airway inflammation is a cardinal feature of chronic obstructive pulmonary disease (COPD), a destructive cigarette smoke-induced lung disease. Although it is apparent that dendritic cells (DCs) are an important constituent of the chronic inflammatory cell influx found in airways of COPD patients, the functional roles of DCs in the pathogenesis of smoking-induced emphysema are unknown. We postulated that DCs activated by cigarette smoke constituents directly participate in the chronic inflammation that characterizes COPD airways. Concordant with this hypothesis, we observed that incubation of DCs with cigarette smoke extract (CSE), and chronic exposure of mice to cigarette smoke, both augmented the generation of neutrophilic chemokines by immature and lipopolysaccharide (LPS) or CD40L-matured DCs. The generation of interleukin-8 (CXCL8/IL-8) by human DCs conditioned with CSE was suppressed by the anti-oxidant n-acetyl cysteine (NAC), implying the involvement of oxidant sensitive pathways as a primary mechanism involved in the enhanced CXCL8/IL-8 generation. Cigarette smoke extract and nicotine also augment the production of secreted prostaglandin-E2 and intra-cellular cyclo-oxygenase-2 (COX-2) in maturing DCs. Whereas NAC suppressed production of CXCL8 by CSE-conditioned DCs, it augmented production of PGE2 and cellular COX-2 levels in maturing DCs. These studies indicate that the stimulation of DCs by cigarette smoke-induced oxidative stress and nicotine promote the generation of pro-inflammatory responses that promote chronic inflammation in smokers. Certain pharmacologic strategies such as anti-oxidant therapy may be only partially effective in mitigating cigarette smoke-induced pro-inflammatory DC-mediated responses in smokers.

Original languageEnglish (US)
Pages (from-to)3321-3329
Number of pages9
JournalMolecular Immunology
Volume45
Issue number12
DOIs
StatePublished - Jul 2008

Keywords

  • Chemokines
  • Dendritic cell
  • Neutrophil
  • Oxidative stress
  • Prostaglandins
  • Smoking

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

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