Aspirin-triggered resolvin D1 reduces mucosal inflammation and promotes resolution in a murine model of acute lung injury

O. Eickmeier, H. Seki, O. Haworth, J. N. Hilberath, F. Gao, M. Uddin, R. H. Croze, T. Carlo, M. A. Pfeffer, B. D. Levy

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115 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)256-266
Number of pages11
JournalMucosal Immunology
Volume6
Issue number2
DOIs
Publication statusPublished - 2013 Mar 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Eickmeier, O., Seki, H., Haworth, O., Hilberath, J. N., Gao, F., Uddin, M., Croze, R. H., Carlo, T., Pfeffer, M. A., & Levy, B. D. (2013). Aspirin-triggered resolvin D1 reduces mucosal inflammation and promotes resolution in a murine model of acute lung injury. Mucosal Immunology, 6(2), 256-266. https://doi.org/10.1038/mi.2012.66