Inflammation Research

, Volume 60, Issue 5, pp 409–424

Impact of smoking on inflammation: overview of molecular mechanisms

  • R. B. Gonçalves
  • R. D. Coletta
  • K. G. Silvério
  • L. Benevides
  • M. Z. Casati
  • J. S. da Silva
  • F. H. NocitiJr.



Inflammation is a critical component of normal tissue repair, as well as being fundamental to the body’s defense against infection. Environmental factors, such as smoking, have been reported to modify the host response and hence modify inflammation progression, severity and outcome. Therefore, a comprehensive understanding of the molecular mechanisms by which smoking affects inflammation is vital for preventive and therapeutic strategies on a clinical level.


The purpose of the present article is to review the potential biological mechanisms by which smoking affects inflammation, emphasizing recent developments.


Smoking is reported to effect a number of biological mediators of inflammation through its effect on immune-inflammatory cells, leading to an immunosuppressant state. Recent evidence strongly suggests that the molecular mechanisms behind the modulation of inflammation by smoking mainly involve the nuclear factor-kappa B (NF-kB) family, through the activation of both an inhibitor of IkB kinase (IKK)-dependent and -independent pathway. In addition to NF-kB activation, a number of transcriptional factors including GATA, PAX5 and Smad 3/4, have also been implicated.


Multiple mechanisms may be responsible for the association of smoking and inflammation, and the identification of potential therapeutic targets should guide future research.


Cigarette smoking Inflammation Immune system Periodontal disease Nicotine Cholinergic 


  1. 1.
    Sopori M. Effects of cigarette smoke on the immune system. Nat Rev Immunol. 2002;2:372–7.PubMedGoogle Scholar
  2. 2.
    Barbour SE, Nakashima K, Zhang JB, Tangada S, Hahn CL, Schenkein HA. Tobacco and smoking: environmental factors that modify the host response (immune system) and have an impact on periodontal health. Crit Rev Oral Biol Med. 1997;8:437–60.PubMedGoogle Scholar
  3. 3.
    Kinane DF, Chestnutt IG. Smoking and periodontal disease. Crit Rev Oral Biol Med. 2000;11:356–65.PubMedGoogle Scholar
  4. 4.
    Ryder MI. The influence of smoking on host responses in periodontal infections. Periodontol 2000. 2007;43:267–77.PubMedGoogle Scholar
  5. 5.
    Gualano RC, Hansen MJ, Vlahos R, Jones JE, Park-Jones RA, Deliyannis G, et al. Cigarette smoke worsens lung inflammation and impairs resolution of influenza infection in mice. Respir Res. 2008;9:53.PubMedGoogle Scholar
  6. 6.
    Martorana PA, Lunghi B, Lucattelli M, De Cunto G, Beume R, Lungarella G. Effect of roflumilast on inflammatory cells in the lungs of cigarette smoke-exposed mice. BMC Pulm Med. 2008;8:17.PubMedGoogle Scholar
  7. 7.
    Green GM. Mechanisms of tobacco smoke toxicity on pulmonary macrophage cells. Eur J Respir Dis Suppl. 1985;139:82–5.PubMedGoogle Scholar
  8. 8.
    Kim S, Nadel JA. Role of neutrophils in mucus hypersecretion in COPD and implications for therapy. Treat Respir Med. 2004;3:147–59.PubMedGoogle Scholar
  9. 9.
    Stockley RA. Neutrophils and the pathogenesis of COPD. Chest. 2002;121:151S–5S.PubMedGoogle Scholar
  10. 10.
    Iho S, Tanaka Y, Takauji R, Kobayashi C, Muramatsu I, Iwasaki H, et al. Nicotine induces human neutrophils to produce IL-8 through the generation of peroxynitrite and subsequent activation of NF-kappaB. J Leukoc Biol. 2003;74:942–51.PubMedGoogle Scholar
  11. 11.
    Zappacosta B, Persichilli S, Minucci A, Fasanella S, Scribano D, Giardina B, et al. Effects of aqueous cigarette smoke extract on the chemiluminescence kinetics of polymorphonuclear leukocytes and on their glycolytic and phagocytic activity. Luminescence. 2001;16:315–9.PubMedGoogle Scholar
  12. 12.
    Ryder MI. Nicotine effects on neutrophil F-actin formation and calcium release: implications for tobacco use and pulmonary diseases. Exp Lung Res. 1994;20:283–96.PubMedGoogle Scholar
  13. 13.
    Ogushi F, Hubbard RC, Vogelmeier C, Fells GA, Crystal RG. Risk factors for emphysema. Cigarette smoking is associated with a reduction in the association rate constant of lung alpha I-antitrypsin for neutrophil elastase. J Clin Invest. 1991;87:1060–5.PubMedGoogle Scholar
  14. 14.
    Petropoulos G, McKay I, Hughes F. The association between neutrophil numbers and interleukin-1α concentrations in gingival crevicular fluid of smokers and non-smokers with periodontal disease. J Clin Periodontol. 2004;31:390–5.PubMedGoogle Scholar
  15. 15.
    Pauletto NC, Liede K, Nieminen A, Larjava H, Uitto VJ. Effect of cigarette smoking on oral elastase activity in adult periodontitis patients. J Periodontol. 2000;71:58–62.PubMedGoogle Scholar
  16. 16.
    Kraal JH, Chancellor MB, Bridges RB, Bemis KG, Hawke JE. Variations in the gingival polymorphonuclear leukocyte migration rate in dogs induced by chemotactic autologous serum and migration inhibitor from tobacco smoke. J Periodontal Res. 1977;12:242–9.PubMedGoogle Scholar
  17. 17.
    Ryder MI, Fujutaki R, Lebus S, Mahboub M, Hyum W. Alterations of neutrophil L-selectin and CD18 expression by tobacco smoke: Implications for periodontal diseases. J Periodontol Res. 1998;33:359–68.Google Scholar
  18. 18.
    Güntsch A, Erler M, Preshaw PM, Sigusch BW, Klinger G, Glockmann E. Effect of smoking on crevicular polymorphonuclear neutrophil function in periodontally healthy subjects. J Periodontal Res. 2006;41:184–8.PubMedGoogle Scholar
  19. 19.
    Donaldson K, Brown GM, Drost E, Selby C, MacNee W. Does cigarette smoke enhance the proteolytic activity of neutrophils? Ann NY Acad Sci. 1999;624:325–7.Google Scholar
  20. 20.
    Söder B, Jin LJ, Wickholm S. Granulocyte elastase, matrix metalloproteinase-8 and prostaglandin E2 in gingival crevicular fluid in matched clinical sites in smokers and non-smokers with persistent periodontitis. J Clin Periodontol. 2002;29:384–91.PubMedGoogle Scholar
  21. 21.
    Persson L, Bergström J, Gustafsson A. Effect of tobacco smoking on neutrophil activity following periodontal surgery. J Periodontol. 2003;74:1475–82.PubMedGoogle Scholar
  22. 22.
    Russell RE, Thorley A, Culpitt SV, Dodd S, Donnelly LE, Demattos C, et al. Alveolar macrophage-mediated elastolysis: roles of matrix metalloproteinases, cysteine, and serine proteases. Am J Physiol Lung Cell Mol Physiol. 2002;283:867–73.Google Scholar
  23. 23.
    Hoser G, Domagała-Kulawik J, Droszcz P, Droszcz W, Kawiak J. Lymphocyte subsets differences in smokers and nonsmokers with primary lung cancer: A flow cytometry analysis of broncoalveolar lavage fluid cells. Med Sci Monit. 2003;9:310–5.Google Scholar
  24. 24.
    Hodge S, Hodge G, Ahern J, Jersmann H, Holmes M, Reynolds PN. Smoking alters alveolar macrophage recognition and phagocytic ability: implications in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol. 2007;37:748–55.PubMedGoogle Scholar
  25. 25.
    van der Vaart H, Postma DS, Timens W, ten Hacken NH. Acute effects of cigarette smoke on inflammation and oxidative stress: a review. Thorax. 2004;59:713–21.PubMedGoogle Scholar
  26. 26.
    Berenson CS, Garlipp MA, Grove LJ, Maloney J, Sethi S. Impaired phagocytosis of nontypeable Haemophilus influenzae by human alveolar macrophages in chronic obstructive pulmonary disease. J Infect Dis. 2006;194:1375–84.PubMedGoogle Scholar
  27. 27.
    Chen H, Cowan MJ, Hasday JD, Vogel SN, Medvedev AE. Tobacco smoking inhibits expression of proinflammatory cytokines and activating of IL-1R-associated kinase, p38, and NF-κB in alveolar macrophages stimulates with TLR2 and TLR4 agonists. J Immunol. 2007;179:6097–106.PubMedGoogle Scholar
  28. 28.
    Gaschler GJ, Zavitz CC, Bauer CM, Skrtic M, Lindahl M, Robbins CS, et al. Cigarette smoke exposure attenuates cytokine production by mouse alveolar macrophages. Am J Respir Cell Mol Biol. 2008;38:218–26.PubMedGoogle Scholar
  29. 29.
    Droemann D, Goldmann T, Tiedje T, Zabel P, Dalhoff K, Schaaf B. Toll-like receptor 2 expression is decreased on alveolar macrophage in cigarette smokers and COPD patients. Respir Res. 2005;6:68.PubMedGoogle Scholar
  30. 30.
    Karimi K, Sarir H, Mortaz E, Smit JJ, Hosseini H, De Kimpe SJ, et al. Toll-like receptor-4 mediates cigarette smoke-induced cytokine production by human macrophages. Respir Res. 2006; 7:66.Google Scholar
  31. 31.
    Doz E, Noulin N, Boichot E, Guénon I, Fick L, Le Bert M, et al. Cigarette smoke-induced pulmonary inflammation is TLR4/MyD88 and IL-1R1/MyD88 signaling dependent. J Immunol. 2008;180:1169–78.PubMedGoogle Scholar
  32. 32.
    Sarir H, Mortaz E, Karimi K, Kraneveld AD, Rahman I, Caldenhoven E, et al. Cigarette smoke regulates the expression of TLR4 and IL-8 production by human macrophages. J Inflamm. 2009;6:12.Google Scholar
  33. 33.
    Noakes PS, Hale J, Thomas R, Lane C, Devadason SG, Prescott SL. Maternal smoking is associated with impaired neonatal toll-like-receptor-mediated immune responses. Eur Respir J. 2006;28:721–9.PubMedGoogle Scholar
  34. 34.
    Drannik AG, Pouladi MA, Robbins CS, Goncharova SI, Kianpour S, Stämpfli MR. Impact of cigarette smoke on clearance and inflammation after Pseudomonas aeruginosa infection. Am J Respir Crit Care Med. 2004;170:1164–71.PubMedGoogle Scholar
  35. 35.
    Mian MF, Lauzon NM, Stampfli MR, Mossman KL, Ashkar AA. Impairment of human NK cell cytotoxic activity and cytokine release by cigarette smoke. J Leukoc Biol. 2008;83:774–84.PubMedGoogle Scholar
  36. 36.
    Ng AK, Travis LB. Subsequent malignant neoplasm in cancer survivors. Cancer J. 2008;14:429–34.PubMedGoogle Scholar
  37. 37.
    Nouri-Shirazi M, Guinet E. A possible mechanism linking cigarette smoke to higher incidence of respiratory infection and asthma. Immunol Lett. 2006;103:167–76.PubMedGoogle Scholar
  38. 38.
    Tsoumakidou M, Demedts IK, Brusselle GG, Jeffery PK. Dendritic cells in chronic obstructive pulmonary disease: new players in an old game. Am J Respir Crit Care Med. 2008;177:1180–6.PubMedGoogle Scholar
  39. 39.
    Jahnsen FL, Strickland DH, Thomas JA, Tobagus IT, Napoli S, Zosky GR, et al. Accelerated antigen sampling and transport by airway mucosal dendritic cells following inhalation of a bacterial stimulus. J Immunol. 2006;177:5861–7.PubMedGoogle Scholar
  40. 40.
    McComb JG, Ranganathan M, Liu XH, Pilewski JM, Ray P, Watkins SC, et al. CX3CL1 up-regulation is associated with recruitment of CX3CR1+ mononuclear phagocytes and T lymphocytes in the lungs during cigarette smoke-induced emphysema. Am J Pathol. 2008;173:949–61.PubMedGoogle Scholar
  41. 41.
    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
  42. 42.
    Yamamoto K, Takanashi S, Hasegawa Y, Kanehira Y, Kaizuka M, Okumura K. Eotaxin level in induced sputum is increased in patients with bronchial asthma and in smokers. Respiration. 2003;70:600–5.PubMedGoogle Scholar
  43. 43.
    Domagała-Kulawik J, Maskey-Warzechowska M, Kraszewska I, Chazan R. The cellular composition and macrophage phenotype in induced sputum in smokers and ex-smokers with COPD. Chest. 2003;123:1054–9.PubMedGoogle Scholar
  44. 44.
    Amin K, Ekberg-Jansson A, Löfdahl CG, Venge P. Relationship between inflammatory cells and structural changes in the lungs of asymptomatic and never smoker: a biopsy study. Thorax. 2003;58:135–42.PubMedGoogle Scholar
  45. 45.
    Small-Howard A, Turner H. Exposure to tobacco-derived materials induces overproduction of secreted proteinases in mast cells. Toxicol Appl Pharmacol. 2005;204:152–63.PubMedGoogle Scholar
  46. 46.
    Mortaz E, Redegeld FA, Sarir H, Karimi K, Raats D, Nijkamp FP, et al. Cigarette smoke stimulates the production of chemokines in mast cells. J Leukoc Biol. 2008;83:575–80.PubMedGoogle Scholar
  47. 47.
    Mortaz E, Folkerts G, Engels F, Nijkamp FP, Redegeld FA. Cigarette smoke suppresses in vitro allergic activation of mouse mast cells. Clin Exp Allergy. 2009;39:679–87.PubMedGoogle Scholar
  48. 48.
    Viau M, Zouali M. B-lymphocytes, innate immunity, and autoimmunity. Clin Immunol. 2005;114:17–26.PubMedGoogle Scholar
  49. 49.
    Gonzalez-Quintela A, Alende R, Gude F, Campos J, Rey J, Meijide LM, et al. Serum levels of immunoglobulins (IgG, IgA, IgM) in a general adult population and their relationship with alcohol consumption, smoking and common metabolic abnormalities. Clin Exp Immunol. 2008;151:42–50.PubMedGoogle Scholar
  50. 50.
    Quinn SM, Zhang JB, Gunsolley JC, Schenkein HA, Tew JG. The influence of smoking and race on adult periodontitis and serum IgG2 levels. J Periodontol. 1998;69:171–7.PubMedGoogle Scholar
  51. 51.
    Tangada SD, Califano JV, Nakashima K, Quinn SM, Zhang JB, Gunsolley JC. The effect of smoking on serum IgG2 reactive with Actinobacillus actinomycetemcomitans in early-onset periodontitis patients. J Periodontol. 1997;68:842–50.PubMedGoogle Scholar
  52. 52.
    Graswinckel JE, van der Velden U, van Winkelhoff AJ, Hoek FJ, Loos BG. Plasma antibody levels in periodontitis patients and controls. J Clin Periodontol. 2004;31:562–8.PubMedGoogle Scholar
  53. 53.
    Al-Ghamdi HS, Anil S. Serum antibody levels in smoker and non-smoker saudi subjects with chronic periodontitis. J Periodontol. 2007;78:1043–50.PubMedGoogle Scholar
  54. 54.
    Zavitz CC, Gaschler GJ, Robbins CS, Botelho FM, Cox PG, Stampfli MR. Impact of cigarette smoke on T and B cell responsiveness. Cell Immunol. 2008;253:38–44.PubMedGoogle Scholar
  55. 55.
    Ishida T, Pinkerton KE, Takeuchi M. Alveolar macrophage from cigarette smoke-exposed mice inhibits B lymphocyte proliferation stimulated with LPS. Respiration. 2009;77:91–5.PubMedGoogle Scholar
  56. 56.
    Mehta H, Nazzal K, Sadikot RT. Cigarette smoking and innate immunity. Inflamm Res. 2008;57:497–503.PubMedGoogle Scholar
  57. 57.
    Maeno T, Houghton AM, Quintero PA, Grumelli S, Owen CA, Shapiro SD. CD8+ T cells are required for inflammation and destruction in cigarettesmoke-induced emphysema in mice. J Immunol. 2007;178:8090–6.PubMedGoogle Scholar
  58. 58.
    Glader P, Möller S, Lilja J, Wieslander E, Löfdahl CG, von Wachenfeldt K. Cigarette smoke extract modulates respiratory defense mechanisms through effects on T-cells and airway epithelial cells. Respir Med. 2006;100:818–27.PubMedGoogle Scholar
  59. 59.
    Avanzini MA, Ricci A, Scaramuzza C, Semino L, Pagella F, Castellazzi AM, et al. Deficiency of INFgamma producing cells in adenoids of children exposed to passive smoke. Int J Immunopathol Pharmacol. 2006;19:609–16.PubMedGoogle Scholar
  60. 60.
    Luppi P, Lain KY, Jeyabalan A, DeLoia JA. The effects of cigarette smoking on circulating maternal leukocytes during pregnancy. Clin Immunol. 2007;122:214–9.PubMedGoogle Scholar
  61. 61.
    Orbak R, Erciyas K, Kaya H. Flow-cytometric analysis of T-lymphocyte subsets after different treatment methods in smokers and non-smokers with chronic periodontitis. Int Dent J. 2003;53:159–64.PubMedGoogle Scholar
  62. 62.
    Loos BG, Roos MT, Schellekens PT, van der Velden U, Miedema F. Lymphocyte numbers and function in relation to periodontitis and smoking. J Periodontol. 2004;75:557–64.PubMedGoogle Scholar
  63. 63.
    Spira A, Beane J, Shah V, Liu G, Schembri F, Yang X, et al. Effects of cigarette smoke on the human airway epithelial cell transcriptome. Proc Natl Acad Sci USA. 2004;101:10143–8.PubMedGoogle Scholar
  64. 64.
    Phillips J, Kluss B, Richter A, Massey E. Exposure of bronchial epithelial cells to whole cigarette smoke: assessment of cellular responses. Altern Lab Anim. 2005;33:239–48.PubMedGoogle Scholar
  65. 65.
    Floreani AA, Heires AJ, Welniak LA, Miller-Lindholm A, Clark-Pierce L, Rennard SI, et al. 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;160:5073–81.PubMedGoogle Scholar
  66. 66.
    Allen-Gipson DS, Floreani AA, Heires AJ, Sanderson SD, MacDonald RG, Wyatt TA. Cigarette smoke extract increases C5a receptor expression in human bronchial epithelial cells. J Pharmacol Exp. 2005;14:476–82.Google Scholar
  67. 67.
    Thaikoottathil JV, Martin RJ, Zdunek J, Weinberger A, Rino JG, Chu HW. Cigarette smoke extract reduces VEGF in primary human airway epithelial cells. Eur Respir J. 2009;33:835–43.PubMedGoogle Scholar
  68. 68.
    Bauer CM, Dewitte-Orr SJ, Hornby KR, Zavitz CC, Lichty BD, Stämpfli MR, et al. Cigarette smoke suppresses type I interferon-mediated antiviral immunity in lung fibroblast and epithelial cells. J Interferon Cytokine Res. 2008;28:167–79.PubMedGoogle Scholar
  69. 69.
    Giannopoulo C, Roehrich N, Mombelli A. Effect of nicotine-treated epithelial cells on the proliferation and collagen production of gingival fibroblasts. J Clin Periodontol. 2001;28:769–75.Google Scholar
  70. 70.
    Peacock ME, Sutherland DE, Schuster GS, Brennan WA, O’Neal RB, Strong SL. The effect of nicotine on reproduction and attachment of human gingival fibroblasts in vitro. J Periodontol. 1993;64:658–65.PubMedGoogle Scholar
  71. 71.
    Ho YC, Chang YC. Regulation of nicotine-induced cyclooxygenase-2 protein expression in human gingival fibroblasts. Acta Pharmacol Sin. 2006;27:409–13.PubMedGoogle Scholar
  72. 72.
    Zhou J, Olson BL, Windsor LJ. Nicotine increases the collagen-degrading ability of human gingival fibroblasts. J Periodontal Res. 2007;42:228–335.PubMedGoogle Scholar
  73. 73.
    Gonzalez R, Arancibia R, Cáceres M, Martínez J, Smith PC. Cigarette smoke condensate stimulates urokinase production through the generation of reactive oxygen species and activation of the mitogen activated protein kinase pathways in human gingival fibroblasts. J Periodontal Res. 2009;44:386–94.PubMedGoogle Scholar
  74. 74.
    Wannamethee SG, Lowe GD, Shaper AG, Rumley A, Lennon L, Whincup PH. Associations between cigarette smoking, pipe/cigar smoking, and smoking cessation, and haemostatic and inflammatory markers for cardiovascular disease. Eur Heart J. 2005;26:1765–73.PubMedGoogle Scholar
  75. 75.
    Bermudez EA, Rifai N, Buring JE, Manson JE, Ridker PM. Relation between markers of systemic vascular inflammation and smoking in women. Am J Cardiol. 2002;89:1117–9.PubMedGoogle Scholar
  76. 76.
    Helmersson J, Larsson A, Vessby B, Basu S. Active smoking and a history of smoking are associated with enhanced prostaglandin F(2alpha), interleukin-6 and F2-isoprostane formation in elderly men. Atherosclerosis. 2005;181:201–7.PubMedGoogle Scholar
  77. 77.
    Meuronen A, Majuri ML, Alenius H, Mäntylä T, Wolff H, Piirilä P, et al. Decreased cytokine and chemokine mRNA expression in bronchoalveolar lavage in asymptomatic smoking subjects. Respiration. 2008;75:450–8.PubMedGoogle Scholar
  78. 78.
    Mishra A, Wang M, Pemmaraju VR, Collins MH, Fulkerson PC, Abonia JP, et al. Esophageal remodeling develops as a consequence of tissue specific IL-5-induced eosinophilia. Gastroenterology. 2008;134:204–14.PubMedGoogle Scholar
  79. 79.
    Boström L, Linder LE, Bergström J. Clinical expression of TNF-alpha in smoking-associated periodontal disease. J Clin Periodontol. 1998;25:767–73.PubMedGoogle Scholar
  80. 80.
    Erdemir EO, Duran I, Haliloglu S. Effects of smoking on clinical parameters and the gingival crevicular fluid levels of IL-6 and TNF-alpha in patients with chronic periodontitis. J Clin Periodontol. 2004;31:99–104.PubMedGoogle Scholar
  81. 81.
    Boström L, Linder LE, Bergström J. Smoking and GCF levels of IL-1beta and IL-1ra in periodontal disease. J Clin Periodontol. 2000;27:250–5.PubMedGoogle Scholar
  82. 82.
    Rawlinson A, Grummitt JM, Walsh TF, Ian Douglas CW. Interleukin 1 and receptor antagonist levels in gingival crevicular fluid in heavy smokers versus non-smokers. J Clin Periodontol. 2003;30:42–8.PubMedGoogle Scholar
  83. 83.
    Almasri A, Wisithphrom K, Windsor LJ, Olson B. Nicotine and lipopolysaccharide affect cytokine expression from gingival fibroblasts. J Periodontol. 2007;78:533–41.PubMedGoogle Scholar
  84. 84.
    César-Neto JB, Duarte PM, de Oliveira MC, Casati MZ, Tambeli CH, Parada CA, et al. Smoking modulates INF-γ expression in the gingival tissues of patients with chronic periodontitis. Eur J Oral Sci. 2006;114:403–8.PubMedGoogle Scholar
  85. 85.
    César-Neto JB, Duarte PM, de Oliveira MC, Tambeli CH, Sallum EA, Nociti FH Jr. Smoking modulates IL-6:IL-10 and RANKL:OPG ratios in the periodontal tissues. J Periodontal Res. 2007;42:184–91.PubMedGoogle Scholar
  86. 86.
    Torres de Heens GL, Kikkert R, Aarden LA, van der Velden U, Loos BG. Effects of smoking on the ex vivo cytokine production in periodontitis. J Periodont Res. 2009;44:28–34.Google Scholar
  87. 87.
    Hasnis E, Bar-Shai M, Burbea Z, Reznick AZ. Mechanisms underlying cigarette smoke-induced NF-kappaB activation in human lymphocytes: the role of reactive nitrogen species. J Physiol Pharmacol. 2007;58:275–87.PubMedGoogle Scholar
  88. 88.
    Szulakowski P, Crowther AJ, Jiménez LA, Donaldson K, Mayer R, Leonard TB, et al. The effect of smoking on the transcriptional regulation of lung inflammation in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2006;174:41–50.PubMedGoogle Scholar
  89. 89.
    Yang SR, Chida AS, Bauter MR, Shafiq N, Seweryniak K, Maggirwar SB, et al. Cigarette smoke induces proinflammatory cytokine release by activation of NF-kappaB and posttranslational modifications of histone deacetylase in macrophages. Am J Physiol Lung Cell Mol Physiol. 2006;291:L46–57.PubMedGoogle Scholar
  90. 90.
    Karin M. The IkappaB kinase—a bridge between inflammation and cancer. Cell Res. 2008;18:334–342.Google Scholar
  91. 91.
    Clement JF, Meloche S, Servant MJ. The IKK-related kinases: from innate immunity to oncogenesis. Cell Res. 2008;18:889–99.PubMedGoogle Scholar
  92. 92.
    Li H, Lin X. Positive and negative signaling components involved in TNFalpha-induced NF-kappaB activation. Cytokine. 2008;41:1–8.PubMedGoogle Scholar
  93. 93.
    Yao H, Yang SR, Kode A, Rajendrasozhan S, Caito S, Adenuga D, et al. Redox regulation of lung inflammation: role of NADPH oxidase and NF-kappaB signalling. Biochem Soc Trans. 2007;35:1151–5.PubMedGoogle Scholar
  94. 94.
    Di Stefano A, Caramori G, Oates T, Capelli A, Lusuardi M, Gnemmi I, et al. Increased expression of nuclear factor-kappaB in bronchial biopsies from smokers and patients with COPD. Eur Respir J. 2002;20:556–63.PubMedGoogle Scholar
  95. 95.
    Yagi O, Aoshiba K, Nagai A. Activation of nuclear factor-kappaB in airway epithelial cells in patients with chronic obstructive pulmonary disease. Respiration. 2006;73:610–6.PubMedGoogle Scholar
  96. 96.
    Zhao J, Harper R, Barchowsky A, Di YP. Identification of multiple MAPK-mediated transcription factors regulated by tobacco smoke in airway epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2007;293:L480–90.PubMedGoogle Scholar
  97. 97.
    Yang SR, Wright J, Bauter M, Seweryniak K, Kode A, Rahman I. Sirtuin regulates cigarette smoke-induced proinflammatory mediator release via RelA/p65 NF-kappaB 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
  98. 98.
    Marwick JA, Kirkham PA, Stevenson CS, Danahay H, Giddings J, Butler K, et al. Cigarette smoke alters chromatin remodeling and induces proinflammatory genes in rat lungs. Am J Respir Cell Mol Biol. 2004;31:633–42.PubMedGoogle Scholar
  99. 99.
    Li YT, He B, Wang YZ. Exposure to cigarette smoke upregulates AP-1 activity and induces TNF-alpha overexpression in mouse lungs. Inhal Toxicol. 2009;21:641–7.PubMedGoogle Scholar
  100. 100.
    Ballina-Rosas M, Tracey KJ. Cholinergic control of inflammation. J Int Med. 2009;265:663–79.Google Scholar
  101. 101.
    Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature. 2000;405:458–62.PubMedGoogle Scholar
  102. 102.
    van Westerloo DJ, Giebelen IA, Florquin S, Daalhuisen J, Bruno MJ, de Vos AF, et al. The cholinergic anti-inflammatory pathway regulates the host response during septic peritonitis. J Infect Dis. 2005;191:2138–48.PubMedGoogle Scholar
  103. 103.
    Waldburger JM, Boyle DL, Pavlov VA, Tracey KJ, Firestein GS. Acetylcholine regulation of synoviocyte cytokine expression by the alpha7 nicotinic receptor. Arthritis Rheum. 2008;58:3439–49.PubMedGoogle Scholar
  104. 104.
    Brioni JD, Decker MW, Sullivan JP, Arneric SP. The pharmacology of (−)nicotine and novel cholinergic channel modulators. Adv Pharmacol. 1997;37:153–214.PubMedGoogle Scholar
  105. 105.
    Wang H, Yu M, Ochnal M, Amella CA, Tanovic M, Susaria S, et al. Nicotinic acetylcholine receptor α7 subunit is an essential regulator of inflammation. Nature. 2003;421:384–7.PubMedGoogle Scholar
  106. 106.
    Mabley J, Gordon S, Pacher P. Nicotine exerts an anti-inflammatory effect in a murine model of acute lung injury. Inflammation 2010. doi:10.1007/s10753-010-9228-x
  107. 107.
    Zhou Y, Zuo X, Li Y, Wang Y, Zhao H, Xiao X. Nicotine inhibits tumor necrosis factor-α induced IL-6 and IL-8 secretion in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Rheumatol Int 2010. doi:10.1007/s00296-010-1549-4
  108. 108.
    Breivik T, Gundersen Y, Gjermo P, von Horsten S, Opstad PK. Nicotinic acethylcholine receptor activation mediates nicotine-induced enhancement of experimental periodontitis. J Periodont Res. 2009;44:110–6.PubMedGoogle Scholar
  109. 109.
    Lerman C, LeSage MG, Perkins KA, O’Malley SS, Siegel SJ, Benowitz NL, et al. Translational research in medication development for nicotine dependence. Nat Rev Drug Discov. 2007;6:746–62.PubMedGoogle Scholar
  110. 110.
    Churg A, Wright JL. Animal models of cigarette smoke-induced chronic obstructive lung disease. Contrib Microbiol. 2007;14:113–25.PubMedGoogle Scholar
  111. 111.
    Quinn SM, Zhang JB, Gunsolley JC, Schenkein JG, Schenkein HA, Tew JG. Influence of smoking and race on immunoglobulin G subclass concentrations in early-onset periodontitis patients. Infect Immun. 1996;64:2500–5.Google Scholar
  112. 112.
    Bostrom L, Linder LE, Bergstrom J. Smoking and crevicular fluid levels of IL-6 and TNF-alpha in periodontal disease. J Clin Periodontol. 1999;26:352–7.Google Scholar

Copyright information

© Springer Basel AG 2011

Authors and Affiliations

  • R. B. Gonçalves
    • 1
  • R. D. Coletta
    • 2
  • K. G. Silvério
    • 3
  • L. Benevides
    • 4
  • M. Z. Casati
    • 3
  • J. S. da Silva
    • 4
  • F. H. NocitiJr.
    • 3
  1. 1.Department of Periodontology and Research Group in Oral Ecology, Faculty of DentistryLaval UniversityQuebec CityCanada
  2. 2.Department of Oral Diagnostics, School of Dentistry at PiracicabaUniversity of CampinasPiracicabaBrazil
  3. 3.Department of Prosthodontics and Periodontics, Division of Periodontics, School of Dentistry at PiracicabaUniversity of CampinasPiracicabaBrazil
  4. 4.Department of Biochemistry and Immunology, School of Medicine of Ribeirão PretoUniversity of São PauloSão PauloBrazil

Personalised recommendations