Establishment of a chronic obstructive pulmonary disease mouse model based on the elapsed time after LPS intranasal instillation

Abstract

Chronic obstructive pulmonary disease (COPD) was the 3^rd 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.