Stromelysin-1 and gelatinase A are upregulated before TNF-alpha in LPS-stimulated neuroinflammation

Brain Research
Sheila Mun-BryceG A Rosenberg

Abstract

Neuroinflammation induces a complex molecular cascade that leads to the proteolysis of cells. Matrix metalloproteinases (MMPs) attack all components of the extracellular matrix in a number of neuroinflammatory diseases and cause a delayed opening of the blood-brain barrier (BBB). Earlier, we showed that lipopolysaccharide (LPS) disrupted the BBB through the action of gelatinase B (MMP-9). In a study of cerebral ischemia, gelatinase A (MMP-2) was seen in astrocytic end-feet and stromelysin-1 (MMP-3) in microglia. Since other MMPs may be important in LPS-induced injury, we studied the gene transcription and cellular localization of several MMPs and an inflammatory mediator, tumor necrosis factor (TNF-alpha), using competitive polymerase chain reaction (PCR) and immunohistochemical methods. Significantly elevated levels of MMP-2 and -3 mRNA were observed in LPS-injected brains by 2 h after injection as compared to non-injected brain tissue (P<0.05). By 8 h post-LPS injection, gene expression of MMP-2 and -3 had declined in both saline- and LPS-injected tissue, while TNF-alpha mRNA levels rose significantly. Immunohistochemistry of control brains confirmed the earlier observation of MMP-2 immunoreactivity in processes abutting cere...Continue Reading

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Citations

Jul 2, 2003·Neurotoxicity Research·Valter R M LombardiRamón Cacabelos
Apr 15, 2006·Digestive Diseases and Sciences·Emily K RobinsonDavid W Mercer
Apr 16, 2009·Clinical Microbiology Reviews·Ineke Vanlaere, Claude Libert
Dec 10, 2003·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Dae-Il ChangGregory J del Zoppo
Dec 10, 2003·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Carles JusticiaAnna M Planas
Oct 16, 2009·Journal of Neuroscience Research·Espen J Walker, Gary A Rosenberg
Dec 20, 2005·The Journal of Surgical Research·Emily K RobinsonDavid W Mercer
Oct 20, 2009·The International Journal of Neuropsychopharmacology·Sabrina GanzinelliLeonor Sterin-Borda
Aug 31, 2002·Glia·Gary A Rosenberg
Nov 4, 2016·International Journal of Molecular Sciences·Inge Van HoveLieve Moons
Jan 31, 2007·Stroke; a Journal of Cerebral Circulation·Gregory J del ZoppoJames A Koziol
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Mar 31, 2004·The Journal of Pharmacology and Experimental Therapeutics·J Fred HessDouglas J Pettibone

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