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- Title
Aspirin-triggered resolvin D1 reduces mucosal inflammation and promotes resolution in a murine model of acute lung injury.
- Authors
Eickmeier, O; Seki, H; Haworth, O; Hilberath, J N; Gao, F; Uddin, M; Croze, R H; Carlo, T; Pfeffer, M A; Levy, B D
- Abstract
Acute lung injury (ALI) is a severe illness with excess mortality and no specific therapy. Protective actions were recently uncovered for docosahexaenoic acid-derived mediators, including D-series resolvins. Here, we used a murine self-limited model of hydrochloric acid-induced ALI to determine the effects of aspirin-triggered resolvin D1 (AT-RvD1; 7S,8R,17R-trihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid) on mucosal injury. RvD1 and its receptor ALX/FPR2 were identified in murine lung after ALI. AT-RvD1 (∼0.5-5 μg kg−1) decreased peak inflammation, including bronchoalveolar lavage fluid (BALF) neutrophils by ∼75%. Animals treated with AT-RvD1 had improved epithelial and endothelial barrier integrity and decreased airway resistance concomitant with increased BALF epinephrine levels. AT-RvD1 inhibited neutrophil-platelet heterotypic interactions by downregulating both P-selectin and its ligand CD24. AT-RvD1 also significantly decreased levels of BALF pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, Kupffer cells, and tumor necrosis factor-α, and decreased nuclear factor-κB-phosphorylated p65 nuclear translocation. Taken together, these findings indicate that AT-RvD1 displays potent mucosal protection and promotes catabasis after ALI.
- Subjects
LUNG injuries; BRONCHOALVEOLAR lavage; PHYSIOLOGICAL effects of aspirin; LABORATORY mice; INTERLEUKIN-1; LEUCOCYTES; MUCUS
- Publication
Mucosal Immunology (1933-0219), 2013, Vol 6, Issue 2, p256
- ISSN
1933-0219
- Publication type
Article
- DOI
10.1038/mi.2012.66