title: Interferon-beta inhibits the expression of metalloproteinases in rat glial cell cultures: implications for multiple sclerosis pathogenesis and treatment.
abstract: Matrix metalloproteinases (MMPs) have been identified as mediators of brain injury in multiple sclerosis (MS) and it has recently been reported that treatment of MS patients with interferon-beta (IFN-beta) reduces MMP-9 serum levels and in vitro release from monocytes. We investigated whether IFN-beta is able to modulate the expression of MMPs in glial cell cultures. Rat microglial and astrocyte cultures were treated with different doses of IFN-beta, then activated by exposure to LPS. In another set of experiments cells were simultaneously activated with LPS and treated with IFN-beta. Culture supernatants collected from astrocytes and microglia were subjected to zymography for the assessment of MMP-2 and MMP-9. Increased amounts of MMP-9 and MMP-2 were observed in supernatants from LPS-treated astrocytes in comparison with supernatants from nontreated control cells. MMP-9 also increased in LPS-treated microglia. The treatment of astrocytes and microglia with IFN-beta inhibited dose-dependently the expression of both MMP-2 and MMP-9 in LPS-treated astrocytes and of MMP-9 in LPS-treated microglia. These results demonstrate a modulating effect of IFN-beta on the release of MMPs from CNS cells. This effect represents an additional mechanism by which IFN-beta, may decrease the development of new CNS lesions in the course of MS.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Bari, 70126 Bari, Italy. m.g.liuzzi@biologia.uniba.it
authors.forename: Grazia Maria
authors.initials: GM
authors.lastname: Liuzzi
authors.forename: Tiziana
authors.initials: T
authors.lastname: Latronico
authors.forename: Anna
authors.initials: A
authors.lastname: Fasano
authors.forename: Giulia
authors.initials: G
authors.lastname: Carlone
authors.forename: Paolo
authors.initials: P
authors.lastname: Riccio
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D002478:Cells, Cultured; D003470:Culture Media / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D016899:Interferon-beta / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats
chemical_list: D000276:Adjuvants, Immunologic; D003470:Culture Media; D012333:RNA, Messenger; D016899:Interferon-beta; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9