TY - JOUR
T1 - Aspirin-triggered resolvin D1 reduces mucosal inflammation and promotes resolution in a murine model of acute lung injury
AU - Eickmeier, O.
AU - Seki, H.
AU - Haworth, O.
AU - Hilberath, J. N.
AU - Gao, F.
AU - Uddin, M.
AU - Croze, R. H.
AU - Carlo, T.
AU - Pfeffer, M. A.
AU - Levy, B. D.
N1 - Funding Information:
We thank GuangLi Zhu and Bonna Ith for technical assistance. This research was supported in part by the US National Institutes of Health grants HL068669, AI068084, and P01-GM095467, and postdoctoral fellowships from the American Lung Association and German Society of Pediatric Pulmonology. The content is solely the responsibility of the authors and does not necessarily reflect the official views of NHLBI, NIAID, NIGMS, or the National Institutes of Health.
PY - 2013/3
Y1 - 2013/3
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84874051649
UR - https://www.scopus.com/pages/publications/84874051649#tab=citedBy
U2 - 10.1038/mi.2012.66
DO - 10.1038/mi.2012.66
M3 - Article
C2 - 22785226
AN - SCOPUS:84874051649
SN - 1933-0219
VL - 6
SP - 256
EP - 266
JO - Mucosal Immunology
JF - Mucosal Immunology
IS - 2
ER -