Abstract
Cigarette smoking is a major cause of chronic obstructive pulmonary disease (COPD). Inhalation of cigarette smoke causes inflammation of the airways, airway wall remodelling, mucus hypersecretion and progressive airflow limitation. Much of the disease burden and health care utilisation in COPD is associated with the management of its comorbidities and infectious (viral and bacterial) exacerbations (AECOPD). Comorbidities, in particular skeletal muscle wasting, cardiovascular disease and lung cancer markedly impact on disease morbidity, progression and mortality. The mechanisms and mediators underlying COPD and its comorbidities are poorly understood and current COPD therapy is relatively ineffective. Many researchers have used animal modelling systems to explore the mechanisms underlying COPD, AECOPD and comorbidities of COPD with the goal of identifying novel therapeutic targets. Here we describe a mouse model that we have developed to define the cellular, molecular and pathological consequences of cigarette smoke exposure and the development of comorbidities of COPD.
References
Vogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, Bourbeau J, Celli BR, Chen R, Decramer M, Fabbri LM, Frith P, Halpin DM, Lopez Varela MV, Nishimura M, Roche N, Rodriguez-Roisin R, Sin DD, Singh D, Stockley R, Vestbo J, Wedzicha JA, Agusti A (2017) Global Strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report: GOLD executive summary. Am J Respir Crit Care Med 195:557–582
Rohde G, Wiethege A, Borg I, Kauth M, Bauer TT, Gillissen A, Bufe A, Schultze-Werninghaus G (2003) Respiratory viruses in exacerbations of chronic obstructive pulmonary disease requiring hospitalisation: a case-control study. Thorax 58:37–42
Sethi S (2004) Bacteria in exacerbations of chronic obstructive pulmonary disease: phenomenon or epiphenomenon? Proc Am Thorac Soc 1:109–114
Seemungal T, Harper-Owen R, Bhowmik A, Moric I, Sanderson G, Message S, Maccallum P, Meade TW, Jeffries DJ, Johnston SL, Wedzicha JA (2001) Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease. Am J Respir Crit Care Med 164:1618–1623
Hurst JR, Vestbo J, Anzueto A, Locantore N, Mullerova H, Tal-Singer R, Miller B, Lomas DA, Agusti A, Macnee W, Calverley P, Rennard S, Wouters EF, Wedzicha JA (2010) Evaluation of CLtIPSEI. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med 363:1128–1138
Barnes PJ, Celli BR (2009) Systemic manifestations and comorbidities of COPD. Eur Respir J 33:1165–1185
Cavailles A, Brinchault-Rabin G, Dixmier A, Goupil F, Gut-Gobert C, Marchand-Adam S, Meurice JC, Morel H, Person-Tacnet C, Leroyer C, Diot P (2013) Comorbidities of COPD. Eur Respir Rev 22:454–475
Maltais F, Decramer M, Casaburi R, Barreiro E, Burelle Y, Debigare R, Dekhuijzen PN, Franssen F, Gayan-Ramirez G, Gea J, Gosker HR, Gosselink R, Hayot M, Hussain SN, Janssens W, Polkey MI, Roca J, Saey D, Schols AM, Spruit MA, Steiner M, Taivassalo T, Troosters T, Vogiatzis I, Wagner PD, ATS/ERS Ad Hoc Committee on Limb Muscle Dysfunction in COPD (2014) An official American Thoracic Society/European Respiratory Society statement: update on limb muscle dysfunction in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 189:e15–e62
Stevenson CS, Birrell MA (2011) Moving towards a new generation of animal models for asthma and COPD with improved clinical relevance. Pharmacol Ther 130:93–105
Vlahos R, Bozinovski S, Gualano RC, Ernst M, Anderson GP (2006) Modelling COPD in mice. Pulm Pharmacol Ther 19:12–17
Stevenson CS, Belvisi MG (2008) Preclinical animal models of asthma and chronic obstructive pulmonary disease. Expert Rev Respir Med 2:631–643
Churg A, Cosio M, Wright JL (2008) Mechanisms of cigarette smoke-induced COPD: insights from animal models. Am J Physiol Lung Cell Mol Physiol 294:L612–L631
Wright JL, Cosio M, Churg A (2008) Animal models of chronic obstructive pulmonary disease. Am J Physiol Lung Cell Mol Physiol 295:L1–15
Wright JL, Churg A (2010) Animal models of cigarette smoke-induced chronic obstructive pulmonary disease. Expert Rev Resp Med 4:723–734
Goldklang MP, Marks SM, D’Armiento JM (2013) Second hand smoke and COPD: lessons from animal studies. Front Physiol 4:30
Vlahos R, Bozinovski S (2014) Recent advances in pre-clinical mouse models of COPD. Clin Sci 126:253–265
Fricker M, Deane A, Hansbro PM (2014) Animal models of chronic obstructive pulmonary disease. Expert Opin Drug Discov 9:629–645
Mercer PF, Abbott-Banner K, Adcock IM, Knowles RG (2015) Translational models of lung disease. Clin Sci 128:235–256
Vlahos R, Bozinovski S (2015) Preclinical murine models of chronic obstructive pulmonary disease. Eur J Pharmacol 759:265–271
Morissette MC, Lamontagne M, Berube JC, Gaschler G, Williams A, Yauk C, Couture C, Laviolette M, Hogg JC, Timens W, Halappanavar S, Stampfli MR, Bosse Y (2014) Impact of cigarette smoke on the human and mouse lungs: a gene-expression comparison study. PLoS One 9:e92498
Vlahos R, Bozinovski S, Jones JE, Powell J, Gras J, Lilja A, Hansen MJ, Gualano RC, Irving L, Anderson GP (2006) Differential protease, innate immunity, and NF-kappaB induction profiles during lung inflammation induced by subchronic cigarette smoke exposure in mice. Am J Physiol Lung Cell Mol Physiol 290:L931–L945
Vlahos R, Bozinovski S, Chan SP, Ivanov S, Linden A, Hamilton JA, Anderson GP (2010) Neutralizing granulocyte/macrophage colony-stimulating factor inhibits cigarette smoke-induced lung inflammation. Am J Respir Crit Care Med 182:34–40
Oostwoud LC, Gunasinghe P, Seow HJ, Ye JM, Selemidis S, Bozinovski S, Vlahos R (2016) Apocynin and ebselen reduce influenza A virus-induced lung inflammation in cigarette smoke-exposed mice. Sci Rep 6:20983
Ruwanpura SM, McLeod L, Miller A, Jones J, Bozinovski S, Vlahos R, Ernst M, Armes J, Bardin PG, Anderson GP, Jenkins BJ (2011) Interleukin-6 promotes pulmonary emphysema associated with apoptosis in mice. Am J Respir Cell Mol Biol 45:720–730
Ruwanpura SM, McLeod L, Miller A, Jones J, Vlahos R, Ramm G, Longano A, Bardin PG, Bozinovski S, Anderson GP, Jenkins BJ (2012) Deregulated Stat3 signaling dissociates pulmonary inflammation from emphysema in gp130 mutant mice. Am J Physiol Lung Cell Mol Physiol 302:L627–L639
Ruwanpura SM, McLeod L, Brooks GD, Bozinovski S, Vlahos R, Longano A, Bardin PG, Anderson GP, Jenkins BJ (2014) IL-6/Stat3-driven pulmonary inflammation, but not emphysema, is dependent on interleukin-17A in mice. Respirology 19:419–427
Ruwanpura SM, McLeod L, Dousha LF, Seow HJ, Alhayyani S, Tate MD, Deswaerte V, Brooks GD, Bozinovski S, MacDonald M, Garbers C, King PT, Bardin PG, Vlahos R, Rose-John S, Anderson GP, Jenkins BJ (2016) Therapeutic targeting of the IL-6 trans-signaling/mechanistic target of rapamycin complex 1 axis in pulmonary emphysema. Am J Respir Crit Care Med 194:1494–1505
Gualano RC, Hansen MJ, Vlahos R, Jones JE, Park-Jones RA, Deliyannis G, Turner SJ, Duca KA, Anderson GP (2008) Cigarette smoke worsens lung inflammation and impairs resolution of influenza infection in mice. Respir Res 9:53
Chen H, Hansen MJ, Jones JE, Vlahos R, Bozinovski S, Anderson GP, Morris MJ (2006) Cigarette smoke exposure reprograms the hypothalamic neuropeptide y axis to promote weight loss. Am J Respir Crit Care Med 173:1248–1254
Chen H, Vlahos R, Bozinovski S, Jones J, Anderson GP, Morris MJ (2005) Effect of short-term cigarette smoke exposure on body weight, appetite and brain neuropeptide Y in mice. Neuropsychopharmacology 30:713–719
Hansen MJ, Gualano RC, Bozinovski S, Vlahos R, Anderson GP (2006) Therapeutic prospects to treat skeletal muscle wasting in COPD (chronic obstructive lung disease). Pharmacol Ther 109:162–172
Chen H, Hansen MJ, Jones JE, Vlahos R, Anderson GP, Morris MJ (2007) Detrimental metabolic effects of combining long-term cigarette smoke exposure and high-fat diet in mice. Am J Physiol Endocrinol Metab 293:E1564–E1571
Hansen MJ, Chen H, Gualano RC, Jones JE, Vlahos R, Morris MJ, Anderson GP (2007) The balance of atrogin-1 and insulin-like growth factor-1 mRNA expression may contribute to wasting after long-term cigarette smoke exposure in mice. Am J Resp Crit Care Med 175:A649
Hansen MJ, Chen H, Jones JE, Langenbach SY, Vlahos R, Gualano RC, Morris MJ, Anderson GP (2013) The lung inflammation and skeletal muscle wasting induced by subchronic cigarette smoke exposure are not altered by a high-fat diet in mice. PLoS One 8:e80471
Acknowledgement
This work was supported by NHMRC Project Grants 1084627 and 1067547.
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Vlahos, R., Bozinovski, S. (2018). Protocols to Evaluate Cigarette Smoke-Induced Lung Inflammation and Pathology in Mice. In: Jenkins, B. (eds) Inflammation and Cancer. Methods in Molecular Biology, vol 1725. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7568-6_5
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DOI: https://doi.org/10.1007/978-1-4939-7568-6_5
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