Establishment of a chronic obstructive pulmonary disease mouse model based on the elapsed time after LPS intranasal instillation
Laboratory Animal Research volume 34, pages 1–10 (2018)
Chronic obstructive pulmonary disease (COPD) was the 3rd leading cause of death in 2012 worldwide. It is particularly severe in the elderly, who are at risk of death by coughing, mucous hypersecretion, and finally breathlessness. Recently, anti-COPD drug development has increased, and many animal screening systems have been studied. Tobacco smoke animal models are the best known animal screening system, but have several preparation requirements, such as a tobacco smoke generator and a separate facility to prevent smoke release. Accordingly, we evaluated the properties of a lipopolysaccharide (LPS) murine model for COPD screening and the effect of the time elapsed from 0 to 72 hr after LPS intranasal instillation on various biomarkers of COPD severity, such as WBC and neutrophils in bronchoalveolar fluid (BALF), IgE in serum, histopathology in the lung, and cytokines (IL-8, TNF-α, IFN-γ, and TGF-β) and chemokines (CCL-2, CXCL1, CXCL9, CXCL10, and CXCL11) in the respiratory system. Although from 48 hr after LPS treatment several factors which could be evaluated as biomarkers for COPD establishment such as WBC and neutrophil in BALF, IgE in serum, cytokines (IL-8, TNF-α, and IFN-γ), and chemokines (CCL-2, CXCL1, CXCL9, CXCL10, and CXCL11) increased at 72 hr the increment of important factors for COPD establishment such as IgE, fibrosis in the lung, and cytokines (IL-8, TNF-α, and IFN-γ) was more clear. Based on our results, we concluded that the optimal time after LPS intranasal instillation is 72 hr.
World Health Organization. November 2016 Chronic obstructive pulmonary disease (COPD), Fact sheet, 2016.
World Health Organization. The top 10 causes of death, Fact sheet No310, 2014.
Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, Buzatu L, Cherniack RM, Rogers RM, Sciurba FC, Coxson HO, Paré PD. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med 2004; 350(26): 26–2645.
Barnes PJ. The cytokine network in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol 2009; 41(6): 6–631.
Hogg JC, Timens W. The pathology of chronic obstructive pulmonary disease. Annu Rev Pathol 2009; 4: 435–459.
Churg A, Cosio M, Wright JL. Mechanisms of cigarette smoke-induced COPD: insights from animal models. Am J Physiol Lung Cell Mol Physiol 2008; 294(4): L612–L631.
Maes T, Provoost S, Lanckacker EA, Cataldo DD, Vanoirbeek JA, Nemery B, Tournoy K G, Joos GF. Mouse models to unravel the role of inhaled pollutants on allergic sensitization and airway inflammation. Respir Res 2010; 11(1): 7.
Birrell MA, Wong S, Hele DJ, McCluskie K, Hardaker E, Belvisi M G. Steroid-resistant inflammation in a rat model of chronic obstructive pulmonary disease is associated with a lack of nuclear factor-kappaB pathway activation. Am J Respir Crit Care Med 2005; 172(1): 1–74.
Håkansson HF, Smailagic A, Brunmark C, Miller-Larsson A, Lal H. Altered lung function relates to inflammation in an acute LPS mouse model. Pulm Pharmacol Ther 2012; 25(5): 5–399.
Bang MA, Seo JH, Seo JW, Jo GH, Jung SK, Yu R, Park DH, Park SJ. Bacillus subtilis KCTC 11782BP-produced alginate oligosaccharide effectively suppresses asthma via T-helper cell type 2-related cytokines. PLos One 2015; 10(7): e0130510.
Gompertz S, O’Brien C, Bayley DL, Hill SL, Stockley RA. Changes in bronchial inflammation during acute exacerbations of chronic bronchitis. Eur Respir J 2001; 17(6): 6–1112.
Samaha HMS, Elsaid AR, NasrEldin E. Total serum IgE level in COPD patients. Egypt J Chest Dis Tuberc 2015; 64(3): 3–573.
America’s Biopharmaceutical Research Companies 2012. Medicines in development COPD, 2012 Report.
Barnes PJ. Immunology of asthma and chronic obstructive pulmonary disease. Nat Rev Immunol 2008; 8(3): 183–192.
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Lee, SY., Cho, JH., Cho, S.S. et al. Establishment of a chronic obstructive pulmonary disease mouse model based on the elapsed time after LPS intranasal instillation. Lab Anim Res 34, 1–10 (2018). https://doi.org/10.5625/lar.2018.34.1.1