Journal Article

Interferon-beta inhibits the expression of metalloproteinases in rat glial cell cultures: implications for multiple sclerosis pathogenesis and treatment

Latronico, Tiziana, Carlone, Giulia, Riccio, Paolo, Liuzzi, Grazia Maria, Fasano, Anna

2004

Overview

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-b) reduces MMP-9 serum levels and in vitro release from monocytes. We investigated whether IFN-b is able to modulate the expression of MMPs in glial cell cultures. Rat microglial and astrocyte cultures were treated with different doses of IFN-b, then activated by exposure to LPS. In another set of experiments cells were simultaneously activated with LPS and treated with IFN-b. C ulture 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-b 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-b on the release of MMPs from C NS cells. This effect represents an additional mechanism by which IFN-b may decrease the development of new C NS lesions in the course of MS.

• Publisher: SAGE Publications,Arnold,Sage Publications Ltd
• Subject: Adjuvants, Immunologic - pharmacology / Animals / Astrocytes - cytology / Astrocytes - drug effects / Astrocytes - enzymology / Biological and medical sciences / Cells, Cultured / Culture Media - metabolism / Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases / Gene Expression Regulation, Enzymologic - drug effects / Immunomodulators / Interferon-beta - pharmacology / Matrix Metalloproteinase 2 - genetics / Matrix Metalloproteinase 2 - metabolism / Matrix Metalloproteinase 9 - genetics / Matrix Metalloproteinase 9 - metabolism / Medical sciences / Microglia - cytology / Microglia - drug effects / Microglia - enzymology / Multiple Sclerosis - drug therapy / Multiple Sclerosis - etiology / Multiple Sclerosis - immunology / Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis / Neurology / Pharmacology. Drug treatments / Rats / RNA, Messenger - analysis