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MMP-3 deficiency alleviates endotoxin-induced acute inflammation in the posterior eye segment

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Abstract
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 (Tnf alpha), 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.
Keywords
LPS, MMP-3, inflammation, retina, blood-retinal barrier, retinal pigment epithelium, leukostasis, BRAIN-BARRIER DISRUPTION, NECROSIS-FACTOR-ALPHA, MATRIX-METALLOPROTEINASE 3, PIGMENT EPITHELIAL-CELLS, LIPOPOLYSACCHARIDE-INDUCED HYPOTHERMIA, OPTICAL COHERENCE TOMOGRAPHY, SIGNAL-TRANSDUCTION PATHWAY, SPINAL-CORD-INJURY, HUMAN RPE CELLS, NF-KAPPA-B

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MLA
Van Hove, Inge, et al. “MMP-3 Deficiency Alleviates Endotoxin-Induced Acute Inflammation in the Posterior Eye Segment.” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol. 17, no. 11, 2016, doi:10.3390/ijms17111825.
APA
Van Hove, I., Lefevere, E., De Groef, L., Sergeys, J., Salinas-Navarro, M., Libert, C., … Moons, L. (2016). MMP-3 deficiency alleviates endotoxin-induced acute inflammation in the posterior eye segment. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 17(11). https://doi.org/10.3390/ijms17111825
Chicago author-date
Van Hove, Inge, Evy Lefevere, Lies De Groef, Jurgen Sergeys, Manuel Salinas-Navarro, Claude Libert, Roosmarijn Vandenbroucke, and Lieve Moons. 2016. “MMP-3 Deficiency Alleviates Endotoxin-Induced Acute Inflammation in the Posterior Eye Segment.” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 17 (11). https://doi.org/10.3390/ijms17111825.
Chicago author-date (all authors)
Van Hove, Inge, Evy Lefevere, Lies De Groef, Jurgen Sergeys, Manuel Salinas-Navarro, Claude Libert, Roosmarijn Vandenbroucke, and Lieve Moons. 2016. “MMP-3 Deficiency Alleviates Endotoxin-Induced Acute Inflammation in the Posterior Eye Segment.” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 17 (11). doi:10.3390/ijms17111825.
Vancouver
1.
Van Hove I, Lefevere E, De Groef L, Sergeys J, Salinas-Navarro M, Libert C, et al. MMP-3 deficiency alleviates endotoxin-induced acute inflammation in the posterior eye segment. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 2016;17(11).
IEEE
[1]
I. Van Hove et al., “MMP-3 deficiency alleviates endotoxin-induced acute inflammation in the posterior eye segment,” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol. 17, no. 11, 2016.
@article{8168094,
  abstract     = {{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 (Tnf alpha), 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.}},
  articleno    = {{1825}},
  author       = {{Van Hove, Inge and Lefevere, Evy and De Groef, Lies and Sergeys, Jurgen and Salinas-Navarro, Manuel and Libert, Claude and Vandenbroucke, Roosmarijn and Moons, Lieve}},
  issn         = {{1422-0067}},
  journal      = {{INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}},
  keywords     = {{LPS,MMP-3,inflammation,retina,blood-retinal barrier,retinal pigment epithelium,leukostasis,BRAIN-BARRIER DISRUPTION,NECROSIS-FACTOR-ALPHA,MATRIX-METALLOPROTEINASE 3,PIGMENT EPITHELIAL-CELLS,LIPOPOLYSACCHARIDE-INDUCED HYPOTHERMIA,OPTICAL COHERENCE TOMOGRAPHY,SIGNAL-TRANSDUCTION PATHWAY,SPINAL-CORD-INJURY,HUMAN RPE CELLS,NF-KAPPA-B}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{23}},
  title        = {{MMP-3 deficiency alleviates endotoxin-induced acute inflammation in the posterior eye segment}},
  url          = {{http://doi.org/10.3390/ijms17111825}},
  volume       = {{17}},
  year         = {{2016}},
}

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