Stromelysin-1 and gelatinase A are upregulated before TNF-alpha in LPS-stimulated neuroinflammation
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
References
Protease production by cultured microglia: substrate gel analysis and immobilized matrix degradation
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