Interplay between Intravitreal RvD1 and Local Endogenous Sirtuin-1 in the Protection from Endotoxin-Induced Uveitis in Rats
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 developmen...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2015/126408 |
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| author | S. Rossi C. Di Filippo C. Gesualdo F. Testa M. C. Trotta R. Maisto B. Ferraro F. Ferraraccio M. Accardo F. Simonelli M. D’Amico |
| author_facet | S. Rossi C. Di Filippo C. Gesualdo F. Testa M. C. Trotta R. Maisto B. Ferraro F. Ferraraccio M. Accardo F. Simonelli M. D’Amico |
| author_sort | S. Rossi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-5c007e9aea2448ffa026aef32d328c51 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-5c007e9aea2448ffa026aef32d328c512025-02-03T01:11:04ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/126408126408Interplay between Intravitreal RvD1 and Local Endogenous Sirtuin-1 in the Protection from Endotoxin-Induced Uveitis in RatsS. Rossi0C. Di Filippo1C. Gesualdo2F. Testa3M. C. Trotta4R. Maisto5B. Ferraro6F. Ferraraccio7M. Accardo8F. Simonelli9M. D’Amico10Department of Ophthalmology, Second University of Naples, 80131 Naples, ItalyDepartment of Experimental Medicine, Second University of Naples, 80138 Naples, ItalyDepartment of Ophthalmology, Second University of Naples, 80131 Naples, ItalyDepartment of Ophthalmology, Second University of Naples, 80131 Naples, ItalyDepartment of Experimental Medicine, Second University of Naples, 80138 Naples, ItalyDepartment of Experimental Medicine, Second University of Naples, 80138 Naples, ItalyDepartment of Experimental Medicine, Second University of Naples, 80138 Naples, ItalyDepartment of Clinical, Public and Preventive Medicine, Second University of Naples, 80138 Naples, ItalyDepartment of Clinical, Public and Preventive Medicine, Second University of Naples, 80138 Naples, ItalyDepartment of Ophthalmology, Second University of Naples, 80131 Naples, ItalyDepartment of Experimental Medicine, Second University of Naples, 80138 Naples, ItalyRat 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.http://dx.doi.org/10.1155/2015/126408 |
| spellingShingle | S. Rossi C. Di Filippo C. Gesualdo F. Testa M. C. Trotta R. Maisto B. Ferraro F. Ferraraccio M. Accardo F. Simonelli M. D’Amico Interplay between Intravitreal RvD1 and Local Endogenous Sirtuin-1 in the Protection from Endotoxin-Induced Uveitis in Rats Mediators of Inflammation |
| title | Interplay between Intravitreal RvD1 and Local Endogenous Sirtuin-1 in the Protection from Endotoxin-Induced Uveitis in Rats |
| title_full | Interplay between Intravitreal RvD1 and Local Endogenous Sirtuin-1 in the Protection from Endotoxin-Induced Uveitis in Rats |
| title_fullStr | Interplay between Intravitreal RvD1 and Local Endogenous Sirtuin-1 in the Protection from Endotoxin-Induced Uveitis in Rats |
| title_full_unstemmed | Interplay between Intravitreal RvD1 and Local Endogenous Sirtuin-1 in the Protection from Endotoxin-Induced Uveitis in Rats |
| title_short | Interplay between Intravitreal RvD1 and Local Endogenous Sirtuin-1 in the Protection from Endotoxin-Induced Uveitis in Rats |
| title_sort | interplay between intravitreal rvd1 and local endogenous sirtuin 1 in the protection from endotoxin induced uveitis in rats |
| url | http://dx.doi.org/10.1155/2015/126408 |
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