Immunologic Research

, Volume 46, Issue 1–3, pp 94–126 | Cite as

Inflammatory response of lung macrophages and epithelial cells to tobacco smoke: a literature review of ex vivo investigations

  • Lauren A. Smith
  • Geraldine M. Paszkiewicz
  • Alan D. Hutson
  • John L. PaulyEmail author


Chronic inflammation contributes to the initiation and progression of tumors and tobacco smoke-associated inflammation is associated with malignant and certain non-neoplastic lung diseases. Reported herein are the results of an interpretative synthesis review of the literature assessing the inflammatory response of lung macrophages (MΦ) and epithelial cells to tobacco smoke as measured ex vivo. Papers were retrieved using Boolean operations from PubMed and Scopus. Many writings reported the results of assays of human MΦ from fresh surgically excised human lung tissue, bronchoalveolar lavage, activated blood monocytes, long-term cell lines and MΦ from different laboratory animals. Some publications reported the findings of comparative studies of lung MΦ freshly isolated from the lungs of smokers and non-smokers. Other papers described the effect of tobacco smoke on lung epithelial cells. Most investigators quantified the response of the target cells to tobacco smoke by measuring the production of pro-inflammatory mediators; these included chemokines, cytokines, reactive oxygen species and enzymes. Investigators have reported conflicting observations of the response of human and animal MΦ and epithelial cells to tobacco smoke. The spectrum included papers describing robust production of various inflammatory mediators, significant reduction of a pro-inflammatory response to a known stimulant and overt cytotoxicity. This literature review documents that there exists no consensus, and no emerging trend line, of the reproducible effect(s) of cigarette smoke. This discrepancy reflects the absence of standardized protocols for collecting, processing and bioassaying the smoke, a highly complex aerosol, and identifies the need for establishing collaborative research schemes.


Chemokines Cytokines Inflammation Lung Macrophages Tobacco smoke 



This research was funded by the NCI Cancer Center Support Grant to the Roswell Park Cancer Institute [CA016056].


  1. 1.
    Nass SJ, Moses HL, editors. Cancer biomarkers—the promises and challenges of improving detection and treatment. Washington, DC:Institute of Medicine, The National Academies Press;2007. 252 p.Google Scholar
  2. 2.
    Engels EA. Inflammation in the development of lung cancer: epidemiological evidence. Expert Rev Anticancer Ther. 2008;8:605–15.PubMedGoogle Scholar
  3. 3.
    Tzortzaki EG, Manbiri I, Vlachaki E, Siafakas NM. Biomarkers in COPD. Curr Med Chem. 2007;14:1037–48.PubMedGoogle Scholar
  4. 4.
    Thacker EL. Lung inflammatory responses. Vet Res. 2006;37:469–86.PubMedGoogle Scholar
  5. 5.
    Nagata M. Inflammatory cells and oxygen radicals. Curr Drug Targets Inflamm Allergy. 2005;4:503–4.PubMedGoogle Scholar
  6. 6.
    Kulinsky VI. Biochemical aspects of inflammation. Biochemistry (Mosc). 2007;72:595–607.Google Scholar
  7. 7.
    Laberge S, El Bassam S. Cytokines, structural cells of the lungs and airway inflammation. Paediatr Respir Rev. 2004;5:S41–5.PubMedGoogle Scholar
  8. 8.
    Azad N, Rojanasakul Y, Yallyathan V. Inflammation and lung cancer: roles of reactive oxygen/nitrogen species. J Toxicol Environ Health B Crit Rev. 2008;11:1–15.PubMedGoogle Scholar
  9. 9.
    Schwartz AG, Prysak GM, Bock CH, Cote ML. The molecular epidemiology of lung cancer. Carcinogenesis. 2007;28:507–18.PubMedGoogle Scholar
  10. 10.
    Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420:860–7.PubMedGoogle Scholar
  11. 11.
    Lawrence T. Inflammation and cancer: a failure of resolution. Trends Pharmacol Sci. 2007;28:162–5.PubMedGoogle Scholar
  12. 12.
    Higashimoto Y, Iwata T, Okada M, Satoh H, Fukuda K, Tohda Y. Serum biomarkers as predictors of lung function decline in chronic obstructive pulmonary disease. Respir Med. 2009;103:1231–8.PubMedGoogle Scholar
  13. 13.
    Comandini A, Rogliani P, Nunziata A, Cazzola M, Curradi G, Saltini C. Biomarkers of lung damage associated with tobacco smoke in induced sputum. Respir Med. 2009;103:1592–613.PubMedGoogle Scholar
  14. 14.
    Collins CD, Purohit S, Podolsky RH, et al. The application of genomic and proteomic technologies in predictive, preventive and personalized medicine. Vascul Pharmacol. 2006;45:258–67.PubMedGoogle Scholar
  15. 15.
    Bonassi S, Ugolini D, Kirsch-Volders M, Strömberg U, Vermeulen R, Tucker JD. Human population studies with cytogenetic biomarkers: review of the literature and future prospectives. Environ Mol Mutagen. 2005;45:258–70.PubMedGoogle Scholar
  16. 16.
    Maruvada P, Wang W, Wagner PD, Srivastava S. Biomarkers in molecular medicine: cancer detection and diagnosis. Biotechniques. 2005;38:S9–15.Google Scholar
  17. 17.
    Scaros O, Fisler R. Biomarker technology roundup: from discovery to clinical applications, a broad set of tools is required to translate from the lab to the clinic. Biotechniques. 2005;38:S30–2.Google Scholar
  18. 18.
    Enewold L, Mechanic LE, Bowman ED, et al. Serum concentrations of cytokines and lung cancer survival in African Americans and Caucasians. Cancer Epidemiol Biomarkers Prev. 2009;18:215–22.PubMedGoogle Scholar
  19. 19.
    van der Vaart H, Postma DS, Timens W, Ten Hacken NHT. Acute effects of cigarette smoke on inflammation and oxidative stress: a review. Thorax. 2004;59:713–21.PubMedGoogle Scholar
  20. 20.
    Yanbaeva DG, Dentener MA, Creutzberg EC, Wesseling G, Wouters EF. Systemic effects of smoking. Chest. 2007;131:1557–66.PubMedGoogle Scholar
  21. 21.
    D’hulst AI, Vermaelen KY, Brusselle GG, Joos GF, Pauwels RA. Time course of cigarette smoke-induced pulmonary inflammation in mice. Eur Respir J. 2005;26:204–13.PubMedGoogle Scholar
  22. 22.
    Kulkarni GS, Nadkarni PP, Cerreta JM, Ma S, Cantor JO. Short-term cigarette smoke exposure potentiates endotoxin-induced pulmonary inflammation. Exp Lung Res. 2007;33:1–13.PubMedGoogle Scholar
  23. 23.
    Spori M. Effects of cigarette smoke on the immune system. Nat Rev Immunol. 2002;2:272–3.Google Scholar
  24. 24.
    Birrell MA, Wong S, Catley MC, Belvisi MG. Impact of tobacco-smoke on key signaling pathways in the innate immune response in lung macrophages. J Cell Physiol. 2008;214:27–37.PubMedGoogle Scholar
  25. 25.
    Doz E, Noulin N, Boichot E, et al. Cigarette smoke-induced pulmonary inflammation is TLR4/MyD88 and IL-1R1/MyD88 signaling dependent. J Immunol. 2008;180:1169–78.PubMedGoogle Scholar
  26. 26.
    Hecht SS. Cigarette smoking: cancer risks, carcinogens, and mechanisms. Langenbecks Arch Surg. 2006;391:603–13.PubMedGoogle Scholar
  27. 27.
    Pauly JL, Allison EA, Hurley EL, Nwogu CE, Wallace PK, Paszkiewicz GM. Fluorescent human lung macrophages analyzed by spectral confocal laser scanning microscopy and multispectral cytometry. Microsc Res Tech. 2005;67:79–89.PubMedGoogle Scholar
  28. 28.
    Streck RJ, Jezewski HM, Rodriquez MI, Hurley EL, Rich GA, Pauly JL. A method for isolating human lung macrophages and observations of autofluorescent phagocytes from the lungs of habitual cigarette smokers. J Immunol Methods. 1994;174:67–82.PubMedGoogle Scholar
  29. 29.
    Thiberville L, Salaün M, Lachkar S, et al. Human in vivo fluorescence microimaging of the alveolar ducts and sacs during bronchoscopy. Eur Respir J. 2009;33:974–85.PubMedGoogle Scholar
  30. 30.
    Aggarwal BB, Shishodia S, Sandur SK, Pandey MK, Sethi G. Inflammation and cancer: how hot is the link? Biochem Pharmacol. 2006;72:1605–21.PubMedGoogle Scholar
  31. 31.
    Choi S, Myers JN. Molecular pathogenesis of oral squamous cell carcinoma: implications for therapy. J Dent Res. 2008;87:14–32.PubMedGoogle Scholar
  32. 32.
    Napier SS, Speight PM. Natural history of potentially malignant oral lesions and conditions: an overview of the literature. J Oral Pathol Med. 2008;37:1–10.PubMedGoogle Scholar
  33. 33.
    Tsantoulis PK, Kastrinakis NG, Tourvas AD, Laskaris G, Gorgoulis VG. Advances in the biology of oral cancer. Oral Oncol. 2007;43:523–34.PubMedGoogle Scholar
  34. 34.
    van Oijen MG, Gilsing MM, Rijksen G, Hordijk GJ, Slootweg PJ. Increased number of proliferating cells in oral epithelium from smokers and ex-smokers. Oral Oncol. 1998;34:297–303.PubMedGoogle Scholar
  35. 35.
    Taybos G. Oral changes associated with tobacco use. Am J Med Sci. 2003;326:179–82.PubMedGoogle Scholar
  36. 36.
    Oliver KG, Kettman JR, Fulton RJ. Multiplexed analysis of human cytokines by use of FlowMetrix system. Clin Chem. 1998;44:2057–60.PubMedGoogle Scholar
  37. 37.
    Hatsukami DK, Joseph AM, Lesage M, et al. Developing the science base for reducing tobacco harm. Nicotine Tob Res. 2007; Suppl 4:S537–53.Google Scholar
  38. 38.
    Parascandola M, Augustson E, O’Connell ME, Marcus S. Consumer awareness and attitudes related to new potential reduced-exposure tobacco product brands. Nicotine Tob Res. 2009;11:886–95.PubMedGoogle Scholar
  39. 39.
    Church TR, Anderson KE, Caporaso NE, et al. A prospectively measured serum biomarker for a tobacco-specific carcinogen and lung cancer in smokers. Cancer Epidemiol Biomarkers Prev. 2009;18:260–6.PubMedGoogle Scholar
  40. 40.
    Gaschler GJ, Zavitz CCJ, Bauer CMT, et al. Cigarette smoke exposure attenuates cytokine production by mouse alveolar macrophages. Am J Respir Cell Mol Biol. 2008;38:216–26.Google Scholar
  41. 41.
    McMaster SK, Paul-Clark MJ, Walters M, Fleet M, et al. Cigarette smoke inhibits macrophage sensing of Gram-negative bacteria and lipopolysaccharide: relative roles of nicotine and oxidant stress. Br J Pharmacol. 2008;153:536–43.PubMedGoogle Scholar
  42. 42.
    Winkler AR, Nocka KH, Sulahian TH, Kobzik L, Williams CM. In vitro modeling of human alveolar macrophages smoke exposure: enhanced inflammation and impaired function. Exp Lung Res. 2008;34:599–629.PubMedGoogle Scholar
  43. 43.
    Facchinetti F, Amadei F, Geppetti P, et al. Alpha, beta-unsaturated aldehydes in cigarette smoke release inflammatory mediators from human macrophages. Am J Respir Cell Mol Biol. 2007;37:617–23.PubMedGoogle Scholar
  44. 44.
    Kang MJ, Homer RJ, Gallo A, et al. IL-18 is induced and IL-18 receptor alpha plays a critical role in the pathogenesis of cigarette smoke-induced pulmonary emphysema and inflammation. J Immunol. 2007;178:1948–59.PubMedGoogle Scholar
  45. 45.
    Lee KM, Renne RA, Harbo SJ, Clark ML, Johnson RE, Gideon KM. 3-Week inhalation exposure to cigarette smoke and/or lipopolysaccharide in AKR/J mice. Inhal Toxicol. 2007;19:23–35.PubMedGoogle Scholar
  46. 46.
    van der Deen M, Timens W, Timmer-Bosscha H, et al. Reduced inflammatory response in cigarette smoke exposed Mrp1/Mdr1a/1b deficient mice. Respir Res. 2007;8:49–56.PubMedGoogle Scholar
  47. 47.
    Yang S, Wright J, Bauter M, Seweryniak K, Kode A, Rahman I. Sirtuin regulates cigarette smoke-induced proinflammatory mediator release via RelA/p65 NK-кB in macrophages in vitro and in rat lungs in vivo: implications for chronic inflammation and aging. Am J Physiol Lung Cell Mol Physiol. 2007;292:L567–76.PubMedGoogle Scholar
  48. 48.
    Karimi K, Sarir H, Mortaz E, et al. Toll-like receptor-4 mediates cigarette smoke-induced cytokine production by human macrophages. Respir Res. 2006;7:66–76.PubMedGoogle Scholar
  49. 49.
    Demirjian L, Abboud RT, Li H, Duronio V. Acute effect of cigarette smoke on TNF-α release by macrophages mediated through the erk1/2 pathway. Biochim Biophys Acta. 2006;1762:592–7.PubMedGoogle Scholar
  50. 50.
    Kubo S, Kobayashi M, Masunaga Y, et al. Cytokine and chemokine expression in cigarette smoke-induced lung injury in guinea pigs. Eur Respir J. 2005;26:993–1001.PubMedGoogle Scholar
  51. 51.
    Nordskog BK, Fields WR, Hellmann GM. Kinetic analysis of cytokine response to cigarette smoke condensate by human endothelial and monocytic cells. Toxicology. 2005;212:87–97.PubMedGoogle Scholar
  52. 52.
    Walters M, Paul-Clark M, McMaster S, Ito K, Adcock I, Mitchell J. Cigarette smoke activates human monocytes by an oxidant AP-1 signaling pathway: Implications for steroid resistance. Mol Pharmacol. 2005;68:1343–53.PubMedGoogle Scholar
  53. 53.
    Castro P, Legora-Machado A, Cardilo-Reis L, et al. Inhibition of interleukin-1β reduces mouse lung inflammation induced by exposure to cigarette smoke. Eur J Pharmacol. 2004;498:279–86.PubMedGoogle Scholar
  54. 54.
    Miller LM, Foster WM, Dambach DM, et al. A murine model of cigarette smoke-induce pulmonary inflammation using intranasally administered smoke-conditioned medium. Exp Lung Res. 2002;28:435–55.PubMedGoogle Scholar
  55. 55.
    Zhang X, Wang L, Zhang H, et al. The effects of cigarette smoke extract on the endothelial production of soluble intercellular adhesion molecule-1 are mediated through macrophages, possible by inducing TNF-α release. Methods Find Exp Clin Pharmacol. 2002;24:261–5.PubMedGoogle Scholar
  56. 56.
    Kyi M, Miyazaki Y, Inoue T, Miyake S, Matsukawa A, Yoshizawa Y. Acute effects of smoke exposure on the cellular and cytokine profile in isolated perfused lungs. Respir Physiol. 2000;123:143–51.PubMedGoogle Scholar
  57. 57.
    Edwards K, Braun KM, Evans G, Sureka AO, Fan S. Mainstream and sidestream cigarette smoke condensates suppress macrophage responsiveness to interferon γ. Hum Exp Toxicol. 1999;18:233–40.PubMedGoogle Scholar
  58. 58.
    Hwang D, Chanmugam P, Boudreau M, Sohn KH, Stone K, Pryor WA. Activation and inactivation of cyclo-oxygenase in rat alveolar macrophages by aqueous cigarette tar extracts. Free Radic Biol Med. 1999;27:i673–82.Google Scholar
  59. 59.
    Braun KM, Cornish T, Valm A, Cundiff J, Pauly JL, Fan S. Immunotoxicology of cigarette smoke condensates: suppression of macrophage responsiveness to interferon γ. Toxicol Appl Pharmacol. 1998;149:136–43.PubMedGoogle Scholar
  60. 60.
    Dubar D, Gosset P, Aerts C, Voisin C, Wallaert B, Tonnel AB. In vitro effects of tobacco smoke on tumor necrosis factor α and interleukin-6 production by alveolar macrophages. Exp Lung Res. 1993;19:345–59.PubMedGoogle Scholar
  61. 61.
    Pessina GP, Paulesu L, Corradeschi F, et al. Production of tumor necrosis factor α by rat alveolar macrophages collected after acute cigarette smoking. Arch Immunol Ther Exp. 1993;41:343–8.Google Scholar
  62. 62.
    Higashimoto Y, Shimada Y, Fukuchi Y, et al. Inhibition of mouse alveolar macrophage production of tumor necrosis factor alpha by acute in vivo and in vitro exposure to tobacco smoke. Respiration. 1992;59:77–80.PubMedGoogle Scholar
  63. 63.
    Tardif J, Borgeat M, Laviolette M. Inhibition of human alveolar macrophage production of leukotriene B4 by acute in vitro and in vivo exposure to tobacco smoke. Am J Respir Cell Mol Biol. 1990;2:155–61.PubMedGoogle Scholar
  64. 64.
    Green GM. Mechanism of tobacco smoke toxicity on pulmonary macrophage cells. Eur J Respir Dis Suppl. 1985;139:82–5.PubMedGoogle Scholar
  65. 65.
    Voisin C, Aerts C, Fournier E, Firlik M. Acute effects of tobacco smoke on alveolar macrophages cultured in gas phase. Eur J Respir Dis. 1985;66:76–81.Google Scholar
  66. 66.
    Shea JW, Huber GL, Holmes L, Homans A. The effect of experimental tobacco smoke inhalation on in vitro alveolar macrophage bactericidal function. J Lab Clin Med. 1978;92:270–82.PubMedGoogle Scholar
  67. 67.
    Guarneri JJ. Influence of acute exposure to cigarette smoke on the alveolar macrophage system. J Lab Clin Med. 1977;89:1215–24.PubMedGoogle Scholar
  68. 68.
    Kent L, Smyth L, Clayton C, Scott L, et al. Cigarette smoke extract induced cytokine and chemokine gene expression changes in COPD macrophages. Cytokine. 2008;42:205–16.PubMedGoogle Scholar
  69. 69.
    Chen H, Cowan MJ, Hasday JD, Vogel SN, Medvedev AE. Tobacco smoking inhibits expression of proinflammatory cytokines and activation of IL-1R-associated kinase, p38, and NF-кB in alveolar macrophages stimulated with TLR2 and TLR4 agonists. J Immunol. 2007;179:6097–106.PubMedGoogle Scholar
  70. 70.
    Koch A, Giembycz M, Stirling RG, et al. Effect of smoking on MAP kinase-induced modulation of IL-8 in human alveolar macrophages. Eur Respir J. 2004;23:805–12.PubMedGoogle Scholar
  71. 71.
    Grasseschi RM, Ramaswamy RB, Levine DJ, Klaassen CD, Wesselius LJ. Cadmium accumulation and detoxification by alveolar macrophages of cigarette smokers. Chest. 2003;124:1924–8.PubMedGoogle Scholar
  72. 72.
    Zeidel A, Beilin B, Yardeni I, Mayburd E, Smirnov G, Bessler H. Immune response in asymptomatic smokers. Acta Anaesthesiol Scand. 2002;46:959–64.PubMedGoogle Scholar
  73. 73.
    Kotani N, Kushikata T, Hashimoto H, Sessler DI, Muraoka M, Matsuki A. Recovery of intraoperative microbicidal and inflammatory functions of alveolar immune cells after a tobacco smoke-free period. Anesthesiology. 2001;94:999–1006.PubMedGoogle Scholar
  74. 74.
    de Boer WI, Sount JK, van Schadewijk A, Stolk J, van Kreiken JH, Hiemstra PS. Monocyte chemoattractant protein 1, interleukin 8, and chronic airways inflammation in COPD. J Pathol. 2000;190:619–26.PubMedGoogle Scholar
  75. 75.
    Lim S, Roche N, Oliver BG, Mattos W, Barnes PJ, Chung KF. Balance of matrix metalloprotease-9 and tissue inhibitor of metalloprotease-1 from alveolar macrophages in cigarette smokers. Regulation by interleukin-10. Am J Respir Crit Care Med. 2000;162:1355–60.PubMedGoogle Scholar
  76. 76.
    Mikuniya T, Nagai S, Tsutsumi T, et al. Proinflammatory or regulatory cytokines released from BALF macrophages of healthy smokers. Respiration. 1999;66:419–26.PubMedGoogle Scholar
  77. 77.
    Ohta T, Yamashita N, Maruyama M, Sugiyama E, Kobayashi M. Cigarette smoking decreases interleukin-8 secretion by human alveolar macrophages. Respir Med. 1998;92:922–7.PubMedGoogle Scholar
  78. 78.
    Staal-van den Brekel AJ, Dentener MA, Drent M, ten Velde GP, Buurman WA, Wouters EF. The enhanced inflammatory response in non-small cell lung carcinoma is not reflected in the alveolar compartment. Respir Med. 1998;92:76–83.PubMedGoogle Scholar
  79. 79.
    Dandrea T, Tu B, Blomberg A, et al. Differential inhibition of inflammatory cytokine release from cultured alveolar macrophages from smokers and non-smokers by NO2. Hum Exp Toxicol. 1997;16:577–88.PubMedGoogle Scholar
  80. 80.
    Wesselius LJ, Nelson ME, Bailey K, O’Brien-Ladner AR. Rapid lung cytokine accumulation and neutrophil recruitment after lipopolysaccharide inhalation by cigarette smokers and non-smokers. J Lab Clin Med. 1997;129:106–14.PubMedGoogle Scholar
  81. 81.
    Kuschner WG, D’Alesssandro A, Wong H, Blanc PD. Dose-dependent cigarette smoking-related inflammatory responses in healthy adults. Eur Respir J. 1996;9:1989–94.PubMedGoogle Scholar
  82. 82.
    Byron KA, Varigos GA, Wootton AM. IL-4 production is increased in cigarette smokers. Clin Exp Immunol. 1994;95:333–6.PubMedCrossRefGoogle Scholar
  83. 83.
    McCrea KA, Ensor JE, Nall K, Bleecker ER, Hasday JD. Altered cytokine regulation in the lungs of cigarette smokers. Am J Respir Crit Care Med. 1994;150:696–703.PubMedGoogle Scholar
  84. 84.
    Janson RW, King TE Jr, Hance KR, Arend WP. Enhanced production of IL-1 receptor antagonist by alveolar macrophages from patients with interstitial lung disease. Am Rev Respir Dis. 1993;148:495–503.PubMedGoogle Scholar
  85. 85.
    Yamaguchi E, Itoh A, Furuya K, Miyamoto H, Abe S, Kawakami Y. Release of tumor necrosis factor-alpha from human alveolar macrophages is decreased in smokers. Chest. 1993;103:479–83.PubMedGoogle Scholar
  86. 86.
    Soliman DM, Twigg HL III. Cigarette smoking decreases bioactive interleukin-6 secretion by alveolar macrophages. Am J Physiol. 1992;263:L471–8.PubMedGoogle Scholar
  87. 87.
    Nagai S, Aung H, Takeuchi M, Kusume K, Izumi T. IL-1 and IL-1 inhibitory activity in the culture supernatants of alveolar macrophages from patients with interstitial lung diseases. Chest. 1991;99:674–80.PubMedGoogle Scholar
  88. 88.
    Brown GP, Iwamoto GK, Monick MM, Hunninghake GW. Cigarette smoking decreases interleukin 1 release by human alveolar macrophages. Am J Physiol. 1989;256:C260–4.PubMedGoogle Scholar
  89. 89.
    Renoux M, Lemarie E. Renoux G: Interleukin-1 secretion by lipopolysaccharide-stimulated alveolar macrophages. Respiration. 1989;55:158–68.PubMedGoogle Scholar
  90. 90.
    Yamaguchi E, Okazaki N, Itoh A, Abe S, Kawakami Y, Okuyama H. Interleukin 1 production by alveolar macrophages is decreased in smokers. Am Rev Respir Dis. 1989;140:397–402.PubMedGoogle Scholar
  91. 91.
    Petersen BH, Steimel LF, Callaghan JT. Suppression of mitogen-induced lymphocyte transformation in cigarette smoke. Clin Immunol Immunopathol. 1983;27:135–40.PubMedGoogle Scholar
  92. 92.
    Betsuyaku T, Hamamura I, Hata J, et al. Bronchiolar chemokine expression is different after single versus repeated cigarette smoke exposure. Respir Res. 2008;9:7–18.PubMedGoogle Scholar
  93. 93.
    Li W, Xu YJ, Shen HH. Effect of cigarette smoke extract on lipopolysaccharide-activated mitogen-activated protein kinase signal transduction pathway in cultured cells. Chin Med J (Engl). 2007;120:1075–81.Google Scholar
  94. 94.
    Glader P, Möller S, Lilja J, Wieslander E, Löfdahl CG, von Wachenfeldt K. Cigarette smoke extract modulates respiratory defence mechanisms through effects on T-cells and airway epithelial cells. Respir Med. 2006;100:818–27.PubMedGoogle Scholar
  95. 95.
    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;24:132–50.Google Scholar
  96. 96.
    Phillips J, Kluss B, Richter A, Massey ED. Exposure of bronchial epithelial cells to whole cigarette smoke: assessment of cellular responses. Altern Lab Anim. 2005;33:239–48.PubMedGoogle Scholar
  97. 97.
    Beisswenger C, Platz J, Siefart C, Vogelmeier C, Bals R. Exposure of differentiated airway epithelial cells to volatile smoke in vitro. Respiration. 2004;71:402–9.PubMedGoogle Scholar
  98. 98.
    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;173:4164–70.PubMedGoogle Scholar
  99. 99.
    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;30:500–9.PubMedGoogle Scholar
  100. 100.
    Hellermann GR, Nagy SB, Kong S, Lockey RF, Mohapatra SS. Mechanism of cigarette smoke condensate-induced acute inflammatory response in human bronchial epithelial cells. Respir Res. 2002;3:22–9.PubMedGoogle Scholar
  101. 101.
    Richter A, O’Donnell RA, Powell RM, et al. 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.PubMedGoogle Scholar
  102. 102.
    Rusznak C, Mills PR, Devalia JL, Sapsford RJ, Davies RJ, Lozewicz S. Effect of cigarette smoke on the permeability and IL-1ß and sICAM-1 release from cultured human bronchial epithelial cells of never-smokers, smokers, and patients with chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol. 2000;23:530–6.PubMedGoogle Scholar
  103. 103.
    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;155:1770–6.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Lauren A. Smith
    • 1
  • Geraldine M. Paszkiewicz
    • 1
  • Alan D. Hutson
    • 2
  • John L. Pauly
    • 1
    Email author
  1. 1.Department of Immunology, Buffalo Life Science Building, L5-306Roswell Park Cancer InstituteBuffaloUSA
  2. 2.Department of BiostatisticsRoswell Park Cancer InstituteBuffaloUSA

Personalised recommendations