title: Immunoresolving actions of oral resolvin D1 include selective regulation of the transcription machinery in resolution-phase mouse macrophages.
abstract: Resolvin D1 (RvD1; 7S,8R,17S-trihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid) is an endogenous immunoresolvent that regulates acute inflammation 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 zymosan A-induced acute peritonitis. Using mathematical resolution indices, RvD1 reduced Ψmax by ∼50%, shortened the resolution interval by 3 h, and significantly reduced total leukocyte (by ∼30-45%) and polymorphonuclear 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 macrophages (MΦs) from the resolution phase of peritonitis, RvD1 down-regulated (by 2- to 3-fold) select genes that control gene transcription, namely coactivator-associated arginine methyltransferase 1 (CARM1), and downstream genes, such as colony-stimulating factor 3, intercellular adhesion molecule 1, and monocyte inflammatory protein 2, which promote neutrophil infiltration and reduce MΦ phagocytosis. Congruently, CARM1 knockdown in human and murine MΦs induced a proresolving phenotype, recapitulating in vivo actions of RvD1. These results establish novel properties of RvD1 and demonstrate that RvD1 modifies the transcription control machinery in MΦs, as part of its mechanisms of action during the resolution of acute inflammation.-Recchiuti, A., Codagnone, M., Pierdomenico, 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.
authors.affiliation: Department of Experimental and Clinical Science, Center of Excellence on Aging, G. d'Annunzio University Foundation, Chieti, Italy a.recchiuti@unich.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Recchiuti
authors.affiliation: Department of Experimental and Clinical Science, Center of Excellence on Aging, G. d'Annunzio University Foundation, Chieti, Italy.
authors.forename: Marilina
authors.initials: M
authors.lastname: Codagnone
authors.affiliation: Department of Medicine and Aging Science, and Center of Excellence on Aging, G. d'Annunzio University Foundation, Chieti, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Pierdomenico
authors.affiliation: Center of Excellence on Aging, G. d'Annunzio University Foundation, Chieti, Italy.
authors.forename: Cosmo
authors.initials: C
authors.lastname: Rossi
authors.affiliation: Center of Excellence on Aging, G. d'Annunzio University Foundation, Chieti, Italy.
authors.forename: Veronica Cecilia
authors.initials: VC
authors.lastname: Mari
authors.affiliation: Department of Medicine and Aging Science, and Center of Excellence on Aging, G. d'Annunzio University Foundation, Chieti, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Cianci
authors.affiliation: Department of Experimental and Clinical Science, Center of Excellence on Aging, G. d'Annunzio University Foundation, Chieti, Italy.
authors.forename: Felice
authors.initials: F
authors.lastname: Simiele
authors.affiliation: Department of Psychological, Humanities and Territorial Sciences, G. d'Annunzio University, Chieti, Italy; and Center of Excellence on Aging, G. d'Annunzio University Foundation, Chieti, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Gatta
authors.affiliation: Department of Experimental and Clinical Science, Center of Excellence on Aging, G. d'Annunzio University Foundation, Chieti, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Romano
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004281:Docosahexaenoic Acids / Q000276:immunology* / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D007962:Leukocytes / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010538:Peritonitis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D014158:Transcription, Genetic / Q000187:drug effects* / Q000235:genetics / Q000276:immunology*
chemical_list: C518399:resolvin D1; D004281:Docosahexaenoic Acids
keywords: chromatin-remodeling enzymes; docosahexaenoic acid; pharmacology