Interferon-beta inhibits the expression of metalloproteinases in rat glial cell cultures: implications for multiple sclerosis pathogenesis and treatment.
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.
Liuzzi
Grazia Maria
GM
Department of Biochemistry and Molecular Biology, University of Bari, 70126 Bari, Italy. m.g.liuzzi@biologia.uniba.it
Latronico
Tiziana
T
Fasano
Anna
A
Carlone
Giulia
G
Riccio
Paolo
P
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
D000276:Adjuvants, Immunologic; D003470:Culture Media; D012333:RNA, Messenger; D016899:Interferon-beta; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9