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BMC Pulmonary Medicine
Published in: BMC Pulmonary Medicine 1/2014

Open Access 01-12-2014 | Research article

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

Authors: David M Comer, Joseph Stuart Elborn, Madeleine Ennis

Published in: BMC Pulmonary Medicine | Issue 1/2014

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Abstract

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.
Appendix
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Literature
1.
Kim JS, Rubin BK: Nasal and sinus inflammation in chronic obstructive pulmonary disease. COPD. 2007, 4: 163-166. 10.1080/15412550701341228.CrossRefPubMed
2.
Mio T, Romberger DJ, Thompson AB, Robbins RA, Heires A, Rennard SI: Cigarette smoke induces interleukin-8 release from human bronchial epithelial cells. Am J Respir Crit Care Med. 1997, 155: 1770-1776. 10.1164/ajrccm.155.5.9154890.CrossRefPubMed
3.
Roberts NJ, Lloyd-Owen SJ, Rapado F, Patel IS, Wilkinson TM, Donaldson GC, Wedzicha JA: Relationship between chronic nasal and respiratory symptoms in patients with COPD. Respir Med. 2003, 97: 909-914. 10.1016/S0954-6111(03)00114-8.CrossRefPubMed
4.
Hurst JR, Wilkinson TM, Donaldson GC, Wedzicha JA: Upper airway symptoms and quality of life in chronic obstructive pulmonary disease (COPD). Respir Med. 2004, 98: 767-770. 10.1016/j.rmed.2004.01.010.CrossRefPubMed
5.
Montnemery P, Svensson C, Adelroth E, Lofdahl CG, Andersson M, Greiff L, Persson CG: Prevalence of nasal symptoms and their relation to self-reported asthma and chronic bronchitis/emphysema. Eur Respir J. 2001, 17: 596-603. 10.1183/09031936.01.17405960.CrossRefPubMed
6.
Lieu JE, Feinstein AR: Confirmations and surprises in the association of tobacco use with sinusitis. Arch Otolaryngol Head Neck Surg. 2000, 126: 940-946. 10.1001/archotol.126.8.940.CrossRefPubMed
7.
Shapiro SD: Smoke gets in your cells. Am J Respir Cell Mol Biol. 2004, 31: 481-482. 10.1165/rcmb.F285.CrossRefPubMed
8.
Sarkar P, Hayes BE: Induction of COX-2 by acrolein in rat lung epithelial cells. Mol Cell Biochem. 2007, 301: 191-199. 10.1007/s11010-007-9411-z.CrossRefPubMed
9.
Zhang H, Forman HJ: Acrolein induces heme oxygenase-1 through PKC-delta and PI3K in human bronchial epithelial cells. Am J Respir Cell Mol Biol. 2008, 38: 483-490. 10.1165/rcmb.2007-0260OC.CrossRefPubMed
10.
McMaster SK, Paul-Clark MJ, Walters M, Fleet M, Anandarajah J, Sriskandan S, Mitchell JA: Cigarette smoke inhibits macrophage sensing of Gram-negative bacteria and lipopolysaccharide: relative roles of nicotine and oxidant stress. Br J Pharmacol. 2008, 153: 536-543. 10.1038/sj.bjp.0707595.CrossRefPubMed
11.
Wang JH, Kim H, Jang YJ: Cigarette smoke extract enhances rhinovirus-induced toll-like receptor 3 expression and interleukin-8 secretion in A549 cells. Am J Rhinol Allergy. 2009, 23: 5-9. 10.2500/ajra.2009.23.3407.CrossRef
12.
Witherden IR, Vanden Bon EJ, Goldstraw P, Ratcliffe C, Pastorino U, Tetley TD: Primary human alveolar type II epithelial cell chemokine release: effects of cigarette smoke and neutrophil elastase. Am J Respir Cell Mol Biol. 2004, 30: 500-509. 10.1165/rcmb.4890.CrossRefPubMed
13.
Koarai A, Yanagisawa S, Sugiura H, Ichikawa T, Akamatsu K, Hirano T, Nakanishi M, Matsunaga K, Minakata Y, Ichinose M: Cigarette smoke augments the expression and responses of toll-like receptor 3 in human macrophages. Respirology. 2012, 17: 1018-1025. 10.1111/j.1440-1843.2012.02198.x.CrossRefPubMed
14.
Floreani AA, Heires AJ, Welniak LA, Miller-Lindholm A, Clark-Pierce L, Rennard SI, Morgan EL, Sanderson SD: Expression of receptors for C5a anaphylatoxin (CD88) on human bronchial epithelial cells: enhancement of C5a-mediated release of IL-8 upon exposure to cigarette smoke. J Immunol. 1998, 160: 5073-5081.PubMed
15.
Betsuyaku T, Hamamura I, Hata J, Takahashi H, Mitsuhashi H, Adair-Kirk TL, Senior RM, Nishimura M: Bronchiolar chemokine expression is different after single versus repeated cigarette smoke exposure. Respir Res. 2008, 9: 7-10.1186/1465-9921-9-7.CrossRefPubMedPubMedCentral
16.
Kode A, Yang SR, Rahman I: Differential effects of cigarette smoke on oxidative stress and proinflammatory cytokine release in primary human airway epithelial cells and in a variety of transformed alveolar epithelial cells. Respir Res. 2006, 7: 132-10.1186/1465-9921-7-132.CrossRefPubMedPubMedCentral
17.
Richter A, O’Donnell RA, Powell RM, Sanders MW, Holgate ST, Djukanovic R, Davies DE: Autocrine ligands for the epidermal growth factor receptor mediate interleukin-8 release from bronchial epithelial cells in response to cigarette smoke. Am J Respir Cell Mol Biol. 2002, 27: 85-90. 10.1165/ajrcmb.27.1.4789.CrossRefPubMed
18.
Laan M, Bozinovski S, Anderson GP: Cigarette smoke inhibits lipopolysaccharide-induced production of inflammatory cytokines by suppressing the activation of activator protein-1 in bronchial epithelial cells. J Immunol. 2004, 173: 4164-4170.CrossRefPubMed
19.
Li W, Xu YJ, Shen HH: Effect of cigarette smoke extract on lipopolysaccha-ride-activated mitogen-activated protein kinase signal transduction pathway in cultured cells. Chin Med J (Engl). 2007, 120: 1075-1081.
20.
Leuchtenberger C, Leuchtenberger R, Zbinden I: Gas vapour phase constituents and SH reactivity of cigarette smoke influence lung cultures. Nature. 1974, 247: 565-567. 10.1038/247565a0.CrossRefPubMed
21.
Fowles J, Dybing E: Application of toxicological risk assessment principles to the chemical constituents of cigarette smoke. Tob Control. 2003, 12: 424-430. 10.1136/tc.12.4.424.CrossRefPubMedPubMedCentral
22.
Li L, Holian A: Acrolein: a respiratory toxin that suppresses pulmonary host defense. Rev Environ Health. 1998, 13: 99-108.PubMed
23.
Jakab GJ: Adverse effect of a cigarette smoke component, acrolein, on pulmonary antibacterial defenses and on viral-bacterial interactions in the lung. Am Rev Respir Dis. 1977, 115: 33-38.PubMed
24.
Costa DL, Kutzman RS, Lehmann JR, Drew RT: Altered lung function and structure in the rat after subchronic exposure to acrolein. Am Rev Respir Dis. 1986, 133: 286-291.PubMed
25.
Caron L, Karkazis K, Raffin TA, Swan G, Koenig BA: Nicotine addiction through a neurogenomic prism: ethics, public health, and smoking. Nicotine Tob Res. 2005, 7: 181-197. 10.1080/14622200500055251.CrossRefPubMedPubMedCentral
26.
Totti N, McCusker KT, Campbell EJ, Griffin GL, Senior RM: Nicotine is chemotactic for neutrophils and enhances neutrophil responsiveness to chemotactic peptides. Science. 1984, 223: 169-171. 10.1126/science.6318317.CrossRefPubMed
27.
Lee LY, Gerhardstein DC, Wang AL, Burki NK: Nicotine is responsible for airway irritation evoked by cigarette smoke inhalation in men. J Appl Physiol. 1955–1961, 1993: 75-
28.
Talhout R, Opperhuizen A, van Amsterdam JG: Role of acetaldehyde in tobacco smoke addiction. Eur Neuropsychopharmacol. 2007, 17: 627-636. 10.1016/j.euroneuro.2007.02.013.CrossRefPubMed
29.
Sisson JH, Tuma DJ, Rennard SI: Acetaldehyde-mediated cilia dysfunction in bovine bronchial epithelial cells. Am J Physiol. 1991, 260: L29-L36.PubMed
30.
Demedts IK, Demoor T, Bracke KR, Joos GF, Brusselle GG: Role of apoptosis in the pathogenesis of COPD and pulmonary emphysema. Respir Res. 2006, 7: 53-10.1186/1465-9921-7-53.CrossRefPubMedPubMedCentral
31.
Hoshino Y, Mio T, Nagai S, Miki H, Ito I, Izumi T: Cytotoxic effects of cigarette smoke extract on an alveolar type II cell-derived cell line. Am J Physiol Lung Cell Mol Physiol. 2001, 281: L509-L516.PubMed
32.
Kim H, Liu X, Kobayashi T, Conner H, Kohyama T, Wen FQ, Fang Q, Abe S, Bitterman P, Rennard SI: Reversible cigarette smoke extract-induced DNA damage in human lung fibroblasts. Am J Respir Cell Mol Biol. 2004, 31: 483-490. 10.1165/rcmb.2002-0300OC.CrossRefPubMed
33.
Lan MY, Ho CY, Lee TC, Yang AH: Cigarette smoke extract induces cytotoxicity on human nasal epithelial cells. Am J Rhinol. 2007, 21: 218-223. 10.2500/ajr.2007.21.2966.CrossRefPubMed
34.
O’Brien GJ, Riddell G, Elborn JS, Ennis M, Skibinski G: Staphylococcus aureus enterotoxins induce IL-8 secretion by human nasal epithelial cells. Respir Res. 2006, 7: 115-10.1186/1465-9921-7-115.CrossRefPubMedPubMedCentral
35.
Comer DM, Elborn JS, Ennis M: Comparison of nasal and bronchial epithelial cells obtained from patients with COPD. PLoS One. 2012, 7: e32924-10.1371/journal.pone.0032924.CrossRefPubMedPubMedCentral
36.
Lee WK, Ramanathan M, Spannhake EW, Lane AP: The cigarette smoke component acrolein inhibits expression of the innate immune components IL-8 and human beta-defensin 2 by sinonasal epithelial cells. Am J Rhinol. 2007, 21: 658-663. 10.2500/ajr.2007.21.3094.CrossRefPubMed
37.
Li L, Hamilton RF, Taylor DE, Holian A: Acrolein-induced cell death in human alveolar macrophages. Toxicol Appl Pharmacol. 1997, 145: 331-339. 10.1006/taap.1997.8189.CrossRefPubMed
38.
Valacchi G, Pagnin E, Phung A, Nardini M, Schock BC, Cross CE, van der Vliet A: Inhibition of NFkappaB activation and IL-8 expression in human bronchial epithelial cells by acrolein. Antioxid Redox Signal. 2005, 7: 25-31. 10.1089/ars.2005.7.25.CrossRefPubMed
39.
Moretto N, Facchinetti F, Southworth T, Civelli M, Singh D, Patacchini R: Alpha, beta-unsaturated aldehydes contained in cigarette smoke elicit IL-8 release in pulmonary cells through mitogen-activated protein kinases. Am J Physiol Lung Cell Mol Physiol. 2009, 296: L839-L848. 10.1152/ajplung.90570.2008.CrossRefPubMed
40.
Greene CM, Ramsay H, Wells RJ, O’Neill SJ, McElvaney NG: Inhibition of Toll-like receptor 2-mediated interleukin-8 production in Cystic Fibrosis airway epithelial cells via the alpha7-nicotinic acetylcholine receptor. Mediators Inflamm. 2010, 2010: 423241-CrossRefPubMedPubMedCentral
41.
Li Q, Zhou X, Kolosov VP, Perelman JM: Nicotine suppresses inflammatory factors in HBE16 airway epithelial cells after exposure to cigarette smoke extract and lipopolysaccharide. Transl Res. 2010, 156: 326-334. 10.1016/j.trsl.2010.09.001.CrossRefPubMed
42.
Tsai JR, Chong IW, Chen CC, Lin SR, Sheu CC, Hwang JJ: Mitogen-activated protein kinase pathway was significantly activated in human bronchial epithelial cells by nicotine. DNA Cell Biol. 2006, 25: 312-322. 10.1089/dna.2006.25.312.CrossRefPubMed
43.
Eiserich JP, van der Vliet A, Handelman GJ, Halliwell B, Cross CE: Dietary antioxidants and cigarette smoke-induced biomolecular damage: a complex interaction. Am J Clin Nutr. 1995, 62: 1490S-1500S.PubMed
44.
Nardini M, Finkelstein EI, Reddy S, Valacchi G, Traber M, Cross CE, van der Vliet A: Acrolein-induced cytotoxicity in cultured human bronchial epithelial cells. Modulation by alpha-tocopherol and ascorbic acid. Toxicology. 2002, 170: 173-185. 10.1016/S0300-483X(01)00540-6.CrossRefPubMed
45.
Yoon CH, Park HJ, Cho YW, Kim EJ, Lee JD, Kang KR, Han J, Kang D: Cigarette smoke extract-induced reduction in migration and contraction in normal human bronchial smooth muscle cells. Korean J Physiol Pharmacol. 2011, 15: 397-403. 10.4196/kjpp.2011.15.6.397.CrossRefPubMedPubMedCentral
46.
Sandborn WJ: Nicotine therapy for ulcerative colitis: a review of rationale, mechanisms, pharmacology, and clinical results. Am J Gastroenterol. 1999, 94: 1161-1171. 10.1111/j.1572-0241.1999.01059.x.CrossRefPubMed
47.
Joe Y, Kim HJ, Kim S, Chung J, Ko MS, Lee WH, Chang KC, Park JW, Chung HT: Tristetraprolin mediates anti-inflammatory effects of nicotine in lipopolysaccharide-stimulated macrophages. J Biol Chem. 2011, 286: 24735-24742. 10.1074/jbc.M110.204859.CrossRefPubMedPubMedCentral
48.
Sugano N, Shimada K, Ito K, Murai S: Nicotine inhibits the production of inflammatory mediators in U937 cells through modulation of nuclear factor-kappaB activation. Biochem Biophys Res Commun. 1998, 252: 25-28. 10.1006/bbrc.1998.9599.CrossRefPubMed
49.
Dowling O, Rochelson B, Way K, Al-Abed Y, Metz CN: Nicotine inhibits cytokine production by placenta cells via NFkappaB: potential role in pregnancy-induced hypertension. Mol Med. 2007, 13: 576-583.CrossRefPubMedPubMedCentral
50.
Cohen C, Bergis OE, Galli F, Lochead AW, Jegham S, Biton B, Leonardon J, Avenet P, Sgard F, Besnard F, Graham D, Coste A, Oblin A, Curet Q, Voltz C, Gardes A, Caille D, Perrault G, George P, Soubrie P, Scatton B: SSR591813, a novel selective and partial alpha4beta2 nicotinic receptor agonist with potential as an aid to smoking cessation. J Pharmacol Exp Ther. 2003, 306: 407-420. 10.1124/jpet.103.049262.CrossRefPubMed
51.
Togo S, Sugiura H, Nelson A, Kobayashi T, Wang X, Kamio K, Kawasaki S, Bitterman P, Rennard SI, Liu X: Hepatic growth factor (HGF) inhibits cigarette smoke extract induced apoptosis in human bronchial epithelial cells. Exp Cell Res. 2010, 316: 3501-3511. 10.1016/j.yexcr.2010.09.006.CrossRefPubMed
52.
Sugiura H, Liu X, Togo S, Kobayashi T, Shen L, Kawasaki S, Kamio K, Wang XQ, Mao LJ, Rennard SI: Prostaglandin E(2) protects human lung fibroblasts from cigarette smoke extract-induced apoptosis via EP(2) receptor activation. J Cell Physiol. 2007, 210: 99-110. 10.1002/jcp.20825.CrossRefPubMed
53.
Manzel LJ, Shi L, O’Shaughnessy PT, Thorne PS, Look DC: Cigarette smoke inhibition of the NF-{kappa}B-dependent response to bacteria in the airway. Am J Respir Cell Mol Biol. 2011, 44: 155-165. 10.1165/rcmb.2009-0454OC.CrossRefPubMed
54.
Liu X, Togo S, Al-Mugotir M, Kim H, Fang Q, Kobayashi T, Wang X, Mao L, Bitterman P, Rennard S: NF-kappaB mediates the survival of human bronchial epithelial cells exposed to cigarette smoke extract. Respir Res. 2008, 9: 66-10.1186/1465-9921-9-66.CrossRefPubMedPubMedCentral
55.
Wickenden JA, Clarke MC, Rossi AG, Rahman I, Faux SP, Donaldson K, MacNee W: Cigarette smoke prevents apoptosis through inhibition of caspase activation and induces necrosis. Am J Respir Cell Mol Biol. 2003, 29: 562-570. 10.1165/rcmb.2002-0235OC.CrossRefPubMed
56.
Groskreutz DJ, Monick MM, Babor EC, Nyunoya T, Varga SM, Look DC, Hunninghake GW: Cigarette smoke alters respiratory syncytial virus-induced apoptosis and replication. Am J Respir Cell Mol Biol. 2009, 41: 189-198. 10.1165/rcmb.2008-0131OC.CrossRefPubMedPubMedCentral
57.
Kaushik G, Kaushik T, Khanduja S, Pathak CM, Khanduja KL: Cigarette smoke condensate promotes cell proliferation through disturbance in cellular redox homeostasis of transformed lung epithelial type-II cells. Cancer Lett. 2008, 270: 120-131. 10.1016/j.canlet.2008.04.039.CrossRefPubMed
58.
Grasl-Kraupp B, Ruttkay-Nedecky B, Koudelka H, Bukowska K, Bursch W, Schulte-Hermann R: In situ detection of fragmented DNA (TUNEL assay) fails to discriminate among apoptosis, necrosis, and autolytic cell death: a cautionary note. Hepatology. 1995, 21: 1465-1468.PubMed
59.
Leist M, Jaattela M: Four deaths and a funeral: from caspases to alternative mechanisms. Nat Rev Mol Cell Biol. 2001, 2: 589-598. 10.1038/35085008.CrossRefPubMed
Metadata
Title
Inflammatory and cytotoxic effects of acrolein, nicotine, acetylaldehyde and cigarette smoke extract on human nasal epithelial cells
Authors
David M Comer
Joseph Stuart Elborn
Madeleine Ennis
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2014
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/1471-2466-14-32

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