title: Resolvin D1 Reduces Emphysema and Chronic Inflammation.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York.
authors.forename: Hsi-Min
authors.initials: HM
authors.lastname: Hsiao
authors.affiliation: Lung Biology and Disease Program, University of Rochester School of Medicine and Dentistry, Rochester, New York; Division of Pulmonary and Critical Care Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Thatcher
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Institutes of Medicine and Harvard Medical School, Boston, Massachusetts.
authors.forename: Romain A
authors.initials: RA
authors.lastname: Colas
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Institutes of Medicine and Harvard Medical School, Boston, Massachusetts.
authors.forename: Charles N
authors.initials: CN
authors.lastname: Serhan
authors.affiliation: Lung Biology and Disease Program, University of Rochester School of Medicine and Dentistry, Rochester, New York; Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Phipps
authors.affiliation: Lung Biology and Disease Program, University of Rochester School of Medicine and Dentistry, Rochester, New York; Division of Pulmonary and Critical Care Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York; Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York. Electronic address: patricia_sime@urmc.rochester.edu.
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Sime
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002908:Chronic Disease; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D006801:Humans; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D011014:Pneumonia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000378:metabolism; D011656:Pulmonary Emphysema / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000502:physiology; D012907:Smoking / Q000009:adverse effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C518399:resolvin D1; D004281:Docosahexaenoic Acids