PMID- 27809288 OWN - NLM STAT- MEDLINE DCOM- 20170410 LR - 20181113 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 17 IP - 11 DP - 2016 Nov 1 TI - MMP-3 Deficiency Alleviates Endotoxin-Induced Acute Inflammation in the Posterior Eye Segment. LID - 1825 AB - 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 alpha (Tnfalpha), 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. FAU - Van Hove, Inge AU - Van Hove I AD - Neural Circuit Development and Regeneration Research Group, Department of Biology, Katholieke Universiteit Leuven (KU Leuven), B-3000 Leuven, Belgium. inge.vanhove@kuleuven.be. AD - Laboratory of Experimental Ophthalmology, Department of Neurosciences, KU Leuven, B-3000 Leuven, Belgium. inge.vanhove@kuleuven.be. FAU - Lefevere, Evy AU - Lefevere E AD - Neural Circuit Development and Regeneration Research Group, Department of Biology, Katholieke Universiteit Leuven (KU Leuven), B-3000 Leuven, Belgium. evy.lefevere@kuleuven.be. AD - Laboratory of Experimental Ophthalmology, Department of Neurosciences, KU Leuven, B-3000 Leuven, Belgium. evy.lefevere@kuleuven.be. FAU - De Groef, Lies AU - De Groef L AD - Neural Circuit Development and Regeneration Research Group, Department of Biology, Katholieke Universiteit Leuven (KU Leuven), B-3000 Leuven, Belgium. lies.degroef@kuleuven.be. AD - Laboratory of Experimental Ophthalmology, Department of Neurosciences, KU Leuven, B-3000 Leuven, Belgium. lies.degroef@kuleuven.be. FAU - Sergeys, Jurgen AU - Sergeys J AD - Neural Circuit Development and Regeneration Research Group, Department of Biology, Katholieke Universiteit Leuven (KU Leuven), B-3000 Leuven, Belgium. jurgen.sergeys@kuleuven.be. AD - Laboratory of Experimental Ophthalmology, Department of Neurosciences, KU Leuven, B-3000 Leuven, Belgium. jurgen.sergeys@kuleuven.be. FAU - Salinas-Navarro, Manuel AU - Salinas-Navarro M AD - Neural Circuit Development and Regeneration Research Group, Department of Biology, Katholieke Universiteit Leuven (KU Leuven), B-3000 Leuven, Belgium. manuel.salinasnavarro@kuleuven.be. FAU - Libert, Claude AU - Libert C AD - Inflammation Research Center, VIB, B-9052 Ghent, Belgium. claude.libert@irc.vib-ugent.be. AD - Department of Biomedical Molecular Biology, Ghent University, B-9052 Ghent, Belgium. claude.libert@irc.vib-ugent.be. FAU - Vandenbroucke, Roosmarijn AU - Vandenbroucke R AD - Inflammation Research Center, VIB, B-9052 Ghent, Belgium. roosmarijn.vandenbroucke@irc.vib-ugent.be. AD - Department of Biomedical Molecular Biology, Ghent University, B-9052 Ghent, Belgium. roosmarijn.vandenbroucke@irc.vib-ugent.be. FAU - Moons, Lieve AU - Moons L AD - Neural Circuit Development and Regeneration Research Group, Department of Biology, Katholieke Universiteit Leuven (KU Leuven), B-3000 Leuven, Belgium. Lieve.moons@kuleuven.be. LA - eng PT - Journal Article DEP - 20161101 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CXCL1) RN - 0 (Icam1 protein, mouse) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - 0 (Tumor Necrosis Factor-alpha) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.13.39 (Nos2 protein, mouse) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Acute Disease MH - Animals MH - Blotting, Western MH - Cell Adhesion/genetics MH - Chemokine CCL2/*genetics/metabolism MH - Chemokine CXCL1/*genetics/metabolism MH - Gene Expression Profiling/methods MH - *Gene Expression Regulation MH - Intercellular Adhesion Molecule-1/genetics/metabolism MH - Interleukin-6/genetics/metabolism MH - Leukocytes/metabolism MH - Lipopolysaccharides MH - Matrix Metalloproteinase 3/deficiency/*genetics MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Nitric Oxide Synthase Type II/genetics/metabolism MH - Retina/metabolism/pathology MH - Retinal Pigment Epithelium/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tomography, Optical Coherence MH - Tumor Necrosis Factor-alpha/genetics/metabolism MH - Uveitis/chemically induced/*genetics/metabolism MH - Vitreous Body/metabolism PMC - PMC5133826 OTO - NOTNLM OT - LPS OT - MMP-3 OT - blood-retinal barrier OT - inflammation OT - leukostasis OT - retina OT - retinal pigment epithelium COIS- The authors declare no conflict of interest. EDAT- 2016/11/04 06:00 MHDA- 2017/04/11 06:00 PMCR- 2016/11/01 CRDT- 2016/11/04 06:00 PHST- 2016/09/29 00:00 [received] PHST- 2016/10/20 00:00 [revised] PHST- 2016/10/25 00:00 [accepted] PHST- 2016/11/04 06:00 [pubmed] PHST- 2017/04/11 06:00 [medline] PHST- 2016/11/04 06:00 [entrez] PHST- 2016/11/01 00:00 [pmc-release] AID - ijms17111825 [pii] AID - ijms-17-01825 [pii] AID - 10.3390/ijms17111825 [doi] PST - epublish SO - Int J Mol Sci. 2016 Nov 1;17(11):1825. doi: 10.3390/ijms17111825.