Resolvin D1 and aspirin-triggered resolvin D1 promote resolution of allergic airways responses.
Asthma is a disease of airway inflammation that in most cases fails to resolve. The resolution of inflammation is an active process governed by specific chemical mediators, including D-series resolvins. In this study, we determined the impact of resolvin D1 (RvD1) and aspirin-triggered RvD1 (AT-RvD1) on the development of allergic airway responses and their resolution. Mice were allergen sensitized, and RvD1, AT-RvD1 (1, 10, or 100 ng), or vehicle was administered at select intervals before or after aerosol allergen challenge. RvD1 markedly decreased airway eosinophilia and mucus metaplasia, in part by decreasing IL-5 and IκBα degradation. For the resolution of established allergic airway responses, AT-RvD1 was even more efficacious than RvD1, leading to a marked decrease in the resolution interval for lung eosinophilia, decrements in select inflammatory peptide and lipid mediators, and more rapid resolution of airway hyperreactivity to methacholine. Relative to RvD1, AT-RvD1 resisted metabolic inactivation by macrophages, and AT-RvD1 significantly enhanced macrophage phagocytosis of IgG-OVA-coated beads in vitro and in vivo, a new proresolving mechanism for the clearance of allergen from the airways. In conclusion, RvD1 and AT-RvD1 can serve as important modulators of allergic airway responses by decreasing eosinophils and proinflammatory mediators and promoting macrophage clearance of allergen. Together, these findings identify D-series resolvins as potential proresolving therapeutic agents for allergic responses.
Pulmonary and Critical Care Medicine Division, Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Alexandre P
AP
Rogerio
Oliver
O
Haworth
Roxanne
R
Croze
Sungwhan F
SF
Oh
Mohib
M
Uddin
Troy
T
Carlo
Michael A
MA
Pfeffer
Rebekah
R
Priluck
Charles N
CN
Serhan
Bruce D
BD
Levy
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000276:immunology* / Q000378:metabolism; D020869:Gene Expression Profiling; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D020033:Protein Isoforms / Q000276:immunology / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines; D020033:Protein Isoforms; C518399:resolvin D1; D004281:Docosahexaenoic Acids; D001241:Aspirin