title: Protection from endotoxic uveitis by intravitreal Resolvin D1: involvement of lymphocytes, miRNAs, ubiquitin-proteasome, and M1/M2 macrophages.
abstract: This study investigated the protective effects of intravitreal Resolvin D1 (RvD1) against LPS-induced rat endotoxic uveitis (EIU). RvD1 was administered into the right eye at a single injection of 5 μL volume containing 10-100-1000 ng/kg RvD1 1 h post-LPS injection (200 μg, Salmonella minnesota) into thefootpad of Sprague-Dawley rats. 24 h later, the eye was enucleated and examined for clinical, biochemical, and immunohistochemical evaluations. RvD1 significantly and dose-dependently decreased the clinical score attributed to EIU, starting from the dose of 10 ng/kg and further decreased by 100 and 1000 ng/kg. These effects were accompanied by changes in four important determinants of the immune-inflammatory response within the eye: (i) the B and T lymphocytes, (ii) the miRNAs pattern, (iii) the ubiquitin-proteasome system (UPS), and (iv) the M1/M2 macrophage phenotype. LPS+RvD1 treated rats showed reduced presence of B and T lymphocytes and upregulation of miR-200c-3p, miR 203a-3p, miR 29b-3p, and miR 21-5p into the eye compared to the LPS alone. This was paralleled by decreases of the ubiquitin, 20S and 26S proteasome subunits, reduced presence of macrophage M1, and increased presence of macrophage M2 in the ocular tissues. Accordingly, the levels of the cytokine TNF-α, the chemokines MIP1-α and NF-κB were reduced.
authors: Multisciplinary Department of Medical-Surgical and Dental Specialities, Second University of Naples, Via Pansini 5, 80131 Naples, Italy.
authors: S
authors: S
authors: Rossi
authors: Section of Pharmacology "L. Donatelli", Department of Experimental Medicine, Second University of Naples, Via Costantinopoli 16, 80138 Naples, Italy.
authors: C
authors: C
authors: Di Filippo
authors: Multisciplinary Department of Medical-Surgical and Dental Specialities, Second University of Naples, Via Pansini 5, 80131 Naples, Italy.
authors: C
authors: C
authors: Gesualdo
authors: DiSTABiF, Second University of Naples, Via Vivaldi 43, 81100 Caserta, Italy.
authors: N
authors: N
authors: Potenza
authors: DiSTABiF, Second University of Naples, Via Vivaldi 43, 81100 Caserta, Italy.
authors: A
authors: A
authors: Russo
authors: Section of Pharmacology "L. Donatelli", Department of Experimental Medicine, Second University of Naples, Via Costantinopoli 16, 80138 Naples, Italy.
authors: M C
authors: MC
authors: Trotta
authors: Section of Pharmacology "L. Donatelli", Department of Experimental Medicine, Second University of Naples, Via Costantinopoli 16, 80138 Naples, Italy.
authors: M V
authors: MV
authors: Zippo
authors: Section of Pharmacology "L. Donatelli", Department of Experimental Medicine, Second University of Naples, Via Costantinopoli 16, 80138 Naples, Italy.
authors: R
authors: R
authors: Maisto
authors: Department of Clinical, Public and Preventive Medicine, Second University of Naples, Via Armanni 5, 80138 Naples, Italy.
authors: F
authors: F
authors: Ferraraccio
authors: Multisciplinary Department of Medical-Surgical and Dental Specialities, Second University of Naples, Via Pansini 5, 80131 Naples, Italy.
authors: F
authors: F
authors: Simonelli
authors: Section of Pharmacology "L. Donatelli", Department of Experimental Medicine, Second University of Naples, Via Costantinopoli 16, 80138 Naples, Italy.
authors: M
authors: M
authors: D'Amico
mesh_terms: D000818:Animals; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D058449:Intravitreal Injections; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D025801:Ubiquitin / Q000378:metabolism*; D014605:Uveitis / Q000517:prevention & control*
chemical_list: D025801:Ubiquitin; C518399:resolvin D1; D004281:Docosahexaenoic Acids; D046988:Proteasome Endopeptidase Complex