Immunoresolving actions of oral resolvin D1 include selective regulation of the transcription machinery in resolution‐phase mouse macrophages

Autor: Eleonora Cianci, Cosmo Rossi, Veronica Cecilia Mari, Anna M Pierdomenico, Felice Simiele, Mario R. Romano, Marilina Codagnone, Antonio Recchiuti, Valentina Gatta
Rok vydání: 2014
Předmět:
Zdroj: The FASEB Journal. 28:3090-3102
ISSN: 1530-6860
0892-6638
DOI: 10.1096/fj.13-248393
Popis: Resolvin D1 (RvD1; 7S,8R,17S-trihydroxy- 4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid) is an en- dogenous immunoresolvent that regulates acute inflam- mation and orchestrates resolution. Here, we investigated anti-inflammatory and proresolving actions of RvD1 after oral administration. RvD1 rapidly accumulated in the mouse plasma after oral delivery and dose-dependently (1-100 ng/mouse) reduced leukocyte infiltration in zymo- san A-induced acute peritonitis. Using mathematical res- olution indices, RvD1 reduced max by 50%, short- ened the resolution interval by 3 h, and significantly reduced total leukocyte (by 30 - 45%) and polymor- phonuclear neutrophil (by 40 -55%) accumulation when administered at the peak of peritonitis. RvD1 also improved course and outcome of severe peritonitis, shifting it toward resolution. In peritoneal macro- phages (Ms) from the resolution phase of peritonitis, RvD1 down-regulated (by 2- to 3-fold) select genes that control gene transcription, namely coactivator-associ- ated arginine methyltransferase 1 (CARM1), and down- stream genes, such as colony-stimulating factor 3, intercellular adhesion molecule 1, and monocyte inflammatory protein 2, which promote neutrophil infiltration and reduce M phagocytosis. Congruently, CARM1 knockdown in human and murine Ms in- duced a proresolving phenotype, recapitulating in vivo actions of RvD1. These results establish novel proper- ties of RvD1 and demonstrate that RvD1 modifies the transcription control machinery in Ms, as part of its mechanisms of action during the resolution of acute inflammation.—Recchiuti, A., Codagnone, M., Pierdo- menico, A. M., Rossi, C., Mari, V. C., Cianci, E., Simiele, F., Gatta, V., Romano, M. Immunoresolving actions of oral resolvin D1 include selective regulation of the transcription machinery in resolution-phase mouse macrophages. FASEB J. 28, 000 - 000 (2014). www.fasebj.org
Databáze: OpenAIRE