Resolvin D1 prevents smoking-induced emphysema and promotes lung tissue regeneration

Abstract

Kang-Hyun Kim,1 Tai Sun Park,2,3 You-Sun Kim,1,3 Jae Seung Lee,2,3 Yeon-Mok Oh,2,3 Sang-Do Lee,2,3 Sei Won Lee2,3 1Asan Institute for Life Sciences, 2Department of Pulmonology and Critical Care Medicine, Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, 3Department of Pulmonology and Critical Care Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea Purpose: Emphysema is an irreversible disease that is characterized by destruction of lung tissue as a result of inflammation caused by smoking. Resolvin D1 (RvD1), derived from docosahexaenoic acid, is a novel lipid that resolves inflammation. The present study tested whether RvD1 prevents smoking-induced emphysema and promotes lung tissue regeneration.Materials and methods: C57BL/6 mice, 8 weeks of age, were randomly divided into four groups: control, RvD1 only, smoking only, and smoking with RvD1 administration. Four different protocols were used to induce emphysema and administer RvD1: mice were exposed to smoking for 4 weeks with poly(I:C) or to smoking only for 24 weeks, and RvD1 was injected within the smoking exposure period to prevent regeneration or after completion of smoking exposure to assess regeneration. The mean linear intercept and inflammation scores were measured in the lung tissue, and inflammatory cells and cytokines were measured in the bronchoalveolar lavage fluid.Results: Measurements of mean linear intercept showed that RvD1 significantly attenuated smoking-induced lung destruction in all emphysema models. RvD1 also reduced smoking-induced inflammatory cell infiltration, which causes the structural derangements observed in emphysema. In the 4-week prevention model, RvD1 reduced the smoking-induced increase in eosinophils and interleukin-6 in the bronchoalveolar lavage fluid. In the 24-week prevention model, RvD1 also reduced the increased neutrophils and total cell counts induced by smoking.Conclusion: RvD1 attenuated smoking-induced emphysema in vivo by reducing inflammation and promoting tissue regeneration. This result suggests that RvD1 may be useful in the prevention and treatment of emphysema. Keywords: resolvin D1, COPD, emphysema

Keywords

• resolvin D1
• chronic obstructive pulmonary disease
• emphysema