Inflammatory and cytotoxic effects of acrolein, nicotine, acetylaldehyde and cigarette smoke extract on human nasal epithelial cells

BMC Pulmonary Medicine

Madeleine Ennis²  Joseph Stuart Elborn¹  David M Comer¹ 

[1] Respiratory Department, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, UK;Centre for Infection and Immunity, Health Sciences Building, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University of Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK

关键词: Apoptosis;    Acetylaldehyde;    Nicotine;    Acrolein;    Cigarette smoke extract;    Nasal epithelium;   

Others  :  866524
DOI  :  10.1186/1471-2466-14-32

 received in 2013-04-10, accepted in 2014-02-25,  发布年份 2014

【 摘 要 】

Background

Cigarette smoke induces a pro-inflammatory response in airway epithelial cells but it is not clear which of the various chemicals contained within cigarette smoke (CS) should be regarded as predominantly responsible for these effects. We hypothesised that acrolein, nicotine and acetylaldehyde, important chemicals contained within volatile cigarette smoke in terms of inducing inflammation and causing addiction, have immunomodulatory effects in primary nasal epithelial cell cultures (PNECs).

Methods

PNECs from 19 healthy subjects were grown in submerged cultures and were incubated with acrolein, nicotine or acetylaldehyde prior to stimulation with Pseudomonas aeruginosa lipopolysaccharide (PA LPS). Experiments were repeated using cigarette smoke extract (CSE) for comparison. IL-8 was measured by ELISA, activation of NF-κB by ELISA and Western blotting, and caspase-3 activity by Western blotting. Apoptosis was evaluated using Annexin-V staining and the terminal transferase-mediated dUTP nick end-labeling (TUNEL) method.

Results

CSE was pro-inflammatory after a 24 h exposure and 42% of cells were apoptotic or necrotic after this exposure time. Acrolein was pro-inflammatory for the PNEC cultures (30 μM exposure for 4 h inducing a 2.0 fold increase in IL-8 release) and also increased IL-8 release after stimulation with PA LPS. In contrast, nicotine had anti-inflammatory properties (0.6 fold IL-8 release after 50 μM exposure to nicotine for 24 h), and acetylaldehyde was without effect. Acrolein and nicotine had cellular stimulatory and anti-inflammatory effects respectively, as determined by NF-κB activation. Both chemicals increased levels of cleaved caspase 3 and induced cell death.

Conclusions

Acrolein is pro-inflammatory and nicotine anti-inflammatory in PNEC cultures. CSE induces cell death predominantly by apoptotic mechanisms.

【 授权许可】

   
2014 Comer et al.; licensee BioMed Central Ltd.

【 图 表 】

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