Title: Resolvin D1 Reduces Emphysema and Chronic Inflammation.

Authors: Hsiao, Hsi-Min; Thatcher, Thomas H; Colas, Romain A; Serhan, Charles N; Phipps, Richard P; Sime, Patricia J

Published In Am J Pathol, (2015 Dec)

Abstract: Chronic obstructive pulmonary disease is characterized, in part, by chronic inflammation that persists even after smoking cessation, suggesting that a failure to resolve inflammation plays an important role in the pathogenesis of the disease. It is widely recognized that the resolution of inflammation is an active process, governed by specialized proresolving lipid mediators, including lipoxins, resolvins, maresins, and protectins. Here, we report that proresolving signaling and metabolic pathways are disrupted in lung tissue from patients with chronic obstructive pulmonary disease, suggesting that supplementation with proresolving lipid mediators might reduce the development of emphysema by controlling chronic inflammation. Groups of mice were exposed long-term to cigarette smoke and treated with the proresolving mediator resolvin D1. Resolvin D1 was associated with a reduced development of cigarette smoke-induced emphysema and airspace enlargement, with concurrent reductions in inflammation, oxidative stress, and cell death. Interestingly, resolvin D1 did not promote the differentiation of M2 macrophages and did not promote tissue fibrosis. Taken together, our results suggest that cigarette smoking disrupts endogenous proresolving pathways and that supplementation with specialized proresolving lipid mediators is an important therapeutic strategy in chronic lung disease, especially if endogenous specialized proresolving lipid mediator signaling is impaired.

PubMed ID: 26468975

MeSH Terms: Adult; Aged; Aged, 80 and over; Animals; Anti-Inflammatory Agents, Non-Steroidal/pharmacology; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use*; Apoptosis/drug effects; Chronic Disease; Docosahexaenoic Acids/metabolism; Docosahexaenoic Acids/pharmacology; Docosahexaenoic Acids/therapeutic use*; Drug Evaluation, Preclinical/methods; Female; Humans; Macrophages, Alveolar/drug effects; Macrophages, Alveolar/pathology; Male; Mice, Inbred C57BL; Middle Aged; Oxidative Stress/drug effects; Pneumonia/metabolism; Pneumonia/pathology; Pneumonia/prevention & control*; Pulmonary Disease, Chronic Obstructive/drug therapy; Pulmonary Disease, Chronic Obstructive/metabolism; Pulmonary Emphysema/metabolism; Pulmonary Emphysema/pathology; Pulmonary Emphysema/prevention & control*; Signal Transduction/physiology; Smoking/adverse effects