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Mediators Inflamm. 2015;2015:149381. doi: 10.1155/2015/149381. Epub 2015 Jan 15.

Protection from endotoxic uveitis by intravitreal Resolvin D1: involvement of lymphocytes, miRNAs, ubiquitin-proteasome, and M1/M2 macrophages.

Author information

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

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.

PMID:
25684860
PMCID:
PMC4312647
DOI:
10.1155/2015/149381
[Indexed for MEDLINE]
Free PMC Article

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