title: Induction of matrix metalloproteinase, cytokines and chemokines in rat cortical astrocytes exposed to plasminogen activators.
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.
authors: Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors: Sun-Ryung
authors: SR
authors: Lee
authors: Shu-Zhen
authors: SZ
authors: Guo
authors: Robert H
authors: RH
authors: Scannevin
authors: Brian C
authors: BC
authors: Magliaro
authors: Kenneth J
authors: KJ
authors: Rhodes
authors: Xiaoying
authors: X
authors: Wang
authors: Eng H
authors: EH
authors: Lo
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism; D005911:Gliosis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000276:immunology* / Q000378:metabolism*; D020767:Intracranial Thrombosis / Q000188:drug therapy; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010960:Plasminogen Activators / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
chemical_list: D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators; D010960:Plasminogen Activators; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9