Next Article in Journal
Pretransplant Levels of CRP and Interleukin-6 Family Cytokines; Effects on Outcome after Allogeneic Stem Cell Transplantation
Next Article in Special Issue
Structure-Functional Basis of Ion Transport in Sodium–Calcium Exchanger (NCX) Proteins
Previous Article in Journal
Cx43 Mediates Resistance against MPP+-Induced Apoptosis in SH-SY5Y Neuroblastoma Cells via Modulating the Mitochondrial Apoptosis Pathway
Previous Article in Special Issue
Experimental Dissection of Metalloproteinase Inhibition-Mediated and Toxic Effects of Phenanthroline on Zebrafish Development
Open AccessArticle

MMP-3 Deficiency Alleviates Endotoxin-Induced Acute Inflammation in the Posterior Eye Segment

1
Neural Circuit Development and Regeneration Research Group, Department of Biology, Katholieke Universiteit Leuven (KU Leuven), B-3000 Leuven, Belgium
2
Laboratory of Experimental Ophthalmology, Department of Neurosciences, KU Leuven, B-3000 Leuven, Belgium
3
Inflammation Research Center, VIB, B-9052 Ghent, Belgium
4
Department of Biomedical Molecular Biology, Ghent University, B-9052 Ghent, Belgium
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Masatoshi Maki
Int. J. Mol. Sci. 2016, 17(11), 1825; https://doi.org/10.3390/ijms17111825
Received: 29 September 2016 / Revised: 20 October 2016 / Accepted: 25 October 2016 / Published: 1 November 2016
(This article belongs to the Special Issue Metalloproteins 2017)
Matrix metalloproteinase-3 (MMP-3) is known to mediate neuroinflammatory processes by activating microglia, disrupting blood–central nervous system barriers and supporting neutrophil influx into the brain. In addition, the posterior part of the eye, more specifically the retina, the retinal pigment epithelium (RPE) and the blood–retinal barrier, is affected upon neuroinflammation, but a role for MMP-3 during ocular inflammation remains elusive. We investigated whether MMP-3 contributes to acute inflammation in the eye using the endotoxin-induced uveitis (EIU) model. Systemic administration of lipopolysaccharide induced an increase in MMP-3 mRNA and protein expression level in the posterior part of the eye. MMP-3 deficiency or knockdown suppressed retinal leukocyte adhesion and leukocyte infiltration into the vitreous cavity in mice subjected to EIU. Moreover, retinal and RPE mRNA levels of intercellular adhesion molecule 1 (Icam1), interleukin 6 (Il6), cytokine-inducible nitrogen oxide synthase (Nos2) and tumor necrosis factor α (Tnfα), which are key molecules involved in EIU, were clearly reduced in MMP-3 deficient mice. In addition, loss of MMP-3 repressed the upregulation of the chemokines monocyte chemoattractant protein (MCP)-1 and (C-X-C motif) ligand 1 (CXCL1). These findings suggest a contribution of MMP-3 during EIU, and its potential use as a therapeutic drug target in reducing ocular inflammation. View Full-Text
Keywords: LPS; MMP-3; inflammation; retina; blood–retinal barrier; retinal pigment epithelium; leukostasis LPS; MMP-3; inflammation; retina; blood–retinal barrier; retinal pigment epithelium; leukostasis
Show Figures

Graphical abstract

MDPI and ACS Style

Van Hove, I.; Lefevere, E.; De Groef, L.; Sergeys, J.; Salinas-Navarro, M.; Libert, C.; Vandenbroucke, R.; Moons, L. MMP-3 Deficiency Alleviates Endotoxin-Induced Acute Inflammation in the Posterior Eye Segment. Int. J. Mol. Sci. 2016, 17, 1825.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop