Abstract
Plasminogen activators are used in thrombolytic stroke therapy. However, it is increasingly recognized that they have other actions besides fibrinolysis. In this study, we assess potential pro-inflammatory effects of tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) in rat cortical astrocytes. Both uPA and tPA induced rapid dose-dependent upregulation in MMP-2 and MMP-9, as demonstrated by zymography of conditioned media. In addition, a multiplex ELISA array demonstrated that patterned responses in chemokines and cytokines were also evoked. Exposure to tPA induced elevations in secreted MIP-2, MCP-1 and GRO/KC. Exposure to uPA induced elevations in secreted IFN-gamma, TNF-alpha, GMCSF, MIP-1alpha, MIP-2, MIP-3alpha, MCP-1, RANTES and fractalkine. These data suggest that plasminogen activators may trigger selected pro-inflammatory responses at the neurovascular interface. Whether these effects influence thrombolytic stroke therapy warrants further investigation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Astrocytes / drug effects*
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Astrocytes / immunology
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Astrocytes / metabolism
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Biomarkers / analysis
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Biomarkers / metabolism
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Blood-Brain Barrier / drug effects
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Blood-Brain Barrier / immunology
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Cells, Cultured
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Cerebral Cortex / drug effects*
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Cerebral Cortex / immunology
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Cerebral Cortex / metabolism
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Chemokines / immunology
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Chemokines / metabolism
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Cytokines / immunology
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Cytokines / metabolism
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Dose-Response Relationship, Drug
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Encephalitis / chemically induced*
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Encephalitis / immunology
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Encephalitis / metabolism
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Gliosis / chemically induced
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Gliosis / immunology
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Gliosis / metabolism
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Inflammation Mediators / immunology*
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Inflammation Mediators / metabolism*
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Intracranial Thrombosis / drug therapy
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Matrix Metalloproteinase 2 / drug effects
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Matrix Metalloproteinase 2 / immunology
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Matrix Metalloproteinase 2 / metabolism
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Matrix Metalloproteinase 9 / drug effects
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Matrix Metalloproteinase 9 / immunology
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Matrix Metalloproteinase 9 / metabolism
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Matrix Metalloproteinases / drug effects
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Matrix Metalloproteinases / immunology
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Matrix Metalloproteinases / metabolism
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Plasminogen Activators / adverse effects*
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Rats
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Rats, Sprague-Dawley
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Up-Regulation / drug effects
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Up-Regulation / immunology
Substances
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Biomarkers
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Chemokines
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Cytokines
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Inflammation Mediators
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Plasminogen Activators
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Matrix Metalloproteinases
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 9