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Am J Pathol. 2015 Dec;185(12):3189-201. doi: 10.1016/j.ajpath.2015.08.008. Epub 2015 Oct 24.

Resolvin D1 Reduces Emphysema and Chronic Inflammation.

Author information

1
Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York.
2
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.
3
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.
4
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.
5
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.

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.

PMID:
26468975
PMCID:
PMC4729265
DOI:
10.1016/j.ajpath.2015.08.008
[Indexed for MEDLINE]
Free PMC Article

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