title: Interplay between Intravitreal RvD1 and Local Endogenous Sirtuin-1 in the Protection from Endotoxin-Induced Uveitis in Rats.
abstract: Rat endotoxin-induced uveitis (EIU) is a well-established model of human uveitis. In this model, intravitreal injection of resolvin D1 (RvD1, 10-100-1000 ng/kg) 1 hour after subcutaneous treatment of Sprague-Dawley rats with lipopolysaccharide (LPS, 200 μg/rat) significantly prevented the development of uveitis into the eye. RvD1 dose-dependently increased the expression of sirtuin-1 (SIRT1) within the eye, while it decreased the expression of acetyl-p53 and acetyl-FOXO1. These effects were accompanied by local downregulation of some microRNAs related to the expression and activity of SIRT1. These were miR-195-5p, miR-200a-3p, miR-34a-5p, and miR-145-5p. An increase of manganese superoxide dismutase and decrease of caspase 3 were evident after RvD1 treatment. In another set of experiments, the protective effects of RvD1 (1000 ng/kg) were partly abolished by the pretreatment of the rats with EX527 (10 mg/kg/day, i.p.), a specific inhibitor of SIRT1 activity, for 7 days prior to the induction of EIU in rats. Similarly, the effects of RvD1 (1000 ng/kg) on the SIRT1 protein expression were abolished by Boc2, N-t-butoxycarbonyl-PLPLP, a specific formyl-peptide receptor type 2/lipoxin A receptor antagonist. Therefore, an interplay of the SIRT1 activity on the RvD1 mediated resolution of EIU is argued.
authors.affiliation: Department of Ophthalmology, Second University of Naples, 80131 Naples, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Rossi
authors.affiliation: Department of Experimental Medicine, Second University of Naples, 80138 Naples, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Di Filippo
authors.affiliation: Department of Ophthalmology, Second University of Naples, 80131 Naples, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Gesualdo
authors.affiliation: Department of Ophthalmology, Second University of Naples, 80131 Naples, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Testa
authors.affiliation: Department of Experimental Medicine, Second University of Naples, 80138 Naples, Italy.
authors.forename: M C
authors.initials: MC
authors.lastname: Trotta
authors.affiliation: Department of Experimental Medicine, Second University of Naples, 80138 Naples, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Maisto
authors.affiliation: Department of Experimental Medicine, Second University of Naples, 80138 Naples, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Ferraro
authors.affiliation: Department of Clinical, Public and Preventive Medicine, Second University of Naples, 80138 Naples, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Ferraraccio
authors.affiliation: Department of Clinical, Public and Preventive Medicine, Second University of Naples, 80138 Naples, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Accardo
authors.affiliation: Department of Ophthalmology, Second University of Naples, 80131 Naples, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Simonelli
authors.affiliation: Department of Experimental Medicine, Second University of Naples, 80138 Naples, Italy.
authors.forename: M
authors.initials: M
authors.lastname: D'Amico
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000032:analysis; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004731:Endotoxins / Q000633:toxicity; D051858:Forkhead Transcription Factors / Q000502:physiology; D058449:Intravitreal Injections; D009419:Nerve Tissue Proteins / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D013482:Superoxide Dismutase / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D014605:Uveitis / Q000517:prevention & control*; D000071161:Forkhead Box Protein O1
chemical_list: D053148:Caspase 3; D004281:Docosahexaenoic Acids; D004731:Endotoxins; D051858:Forkhead Transcription Factors; D009419:Nerve Tissue Proteins; D056564:Sirtuin 1; D013482:Superoxide Dismutase; D016159:Tumor Suppressor Protein p53; C518399:resolvin D1; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1; C488368:Sirt1 protein, rat