| Influence of interleukin-1 beta induction and mitogen-activated protein kinase phosphorylation on optic nerve ligation-induced matrix metalloproteinase-9 activation in the retina. | |
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MedLine Citation:
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PMID: 15037119 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Ischemic damage to the retina is a multifaceted process that results in irreversible loss of ganglion cells and blinding disease. Although the mechanisms underlying ischemia-induced ganglion cell death in the retina are not clearly understood, we have recently reported that retinal damage induced by ligation of the optic nerve results in increased matrix metalloproteinase-9 (MMP-9) synthesis and promotes ganglion cell loss. In this study, we have investigated the roles of IL-1beta and mitogen activated protein kinases in MMP-9 induction in the retina. Optic nerve ligation led to a transient increase in IL-1beta and MMP-9 levels and phosphorylation of p42/p44 mitogen activated protein kinases (extracellular signal-regulated kinases, ERK1 and ERK2) in the retina. We found no significant increase in phosphorylation of p38 MAP kinase or c-jun N-terminal kinases indicating that ERK1/2 plays a major role in MMP-9 induction. Intravitreal injection of IL-1 receptor antagonist (IL-1Ra) or MAP kinase inhibitor U0126 significantly decreased both ERK1/2 phosphorylation and MMP-9 induction suggesting that interruption of this cascade might attenuate retinal damage. In support of this, intravitreal injection of IL-1Ra and U0126 offered significant protection against optic nerve-induced retinal damage. These results suggest that optic nerve ligation-induced IL-1beta promotes retinal damage by increasing MMP-9 synthesis in the retina. |
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Authors:
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Xu Zhang; Shravan K Chintala |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Experimental eye research Volume: 78 ISSN: 0014-4835 ISO Abbreviation: Exp. Eye Res. Publication Date: 2004 Apr |
Date Detail:
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Created Date: 2004-03-23 Completed Date: 2004-05-25 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 0370707 Medline TA: Exp Eye Res Country: England |
Other Details:
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Languages: eng Pagination: 849-60 Citation Subset: IM |
Affiliation:
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Eye Research Institute, Oakland University, 409 Dodge Hall, Rochester, MI 48309, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Western / methods Butadienes / pharmacology Enzyme Activation Enzyme Inhibitors / pharmacology Interleukin-1 / immunology* Matrix Metalloproteinase 9 / metabolism* Mice Mice, Inbred Strains Mitogen-Activated Protein Kinases / antagonists & inhibitors, metabolism* Nitriles / pharmacology Optic Neuropathy, Ischemic / enzymology* Phosphorylation Receptors, Interleukin-1 / metabolism Retina / enzymology* |
| Grant Support | |
ID/Acronym/Agency:
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EY014803/EY/NEI NIH HHS; EY13643/EY/NEI NIH HHS; R01 EY013643-02/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Butadienes; 0/Enzyme Inhibitors; 0/Interleukin-1; 0/Nitriles; 0/Receptors, Interleukin-1; 0/U 0126; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 3.4.24.35/Matrix Metalloproteinase 9 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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