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Mediators of Inflammation
Volume 2015 (2015), Article ID 149381, 12 pages
http://dx.doi.org/10.1155/2015/149381
Research Article

Protection from Endotoxic Uveitis by Intravitreal Resolvin D1: Involvement of Lymphocytes, miRNAs, Ubiquitin-Proteasome, and M1/M2 Macrophages

1Multisciplinary Department of Medical-Surgical and Dental Specialities, Second University of Naples, Via Pansini 5, 80131 Naples, Italy
2Section of Pharmacology “L. Donatelli”, Department of Experimental Medicine, Second University of Naples, Via Costantinopoli 16, 80138 Naples, Italy
3DiSTABiF, Second University of Naples, Via Vivaldi 43, 81100 Caserta, Italy
4Department of Clinical, Public and Preventive Medicine, Second University of Naples, Via Armanni 5, 80138 Naples, Italy

Received 24 June 2014; Revised 13 November 2014; Accepted 8 December 2014

Academic Editor: Marc Pouliot

Copyright © 2015 S. Rossi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.