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Interferon-beta inhibits the expression of metalloproteinases in rat glial cell cultures: implications for multiple
Grazia Maria Liuzzi1, Tiziana Latronico, Anna Fasano
1Department of Biochemistry and Molecular Biology, University of Bari, 70126 Bari, Italy. m.g.liuzzi@biologia.uniba.it
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.
Insights
Interferon-beta (IFN-beta) reduces matrix metalloproteinases (MMPs) in glial cells. This finding suggests a new way IFN-beta may help prevent new central nervous system lesions in multiple sclerosis (MS).
Area of Science:
- Neuroimmunology
- Cellular Biology
Background:
- Matrix metalloproteinases (MMPs) contribute to brain damage in multiple sclerosis (MS).
- Interferon-beta (IFN-beta) treatment in MS patients lowers serum MMP-9 levels and monocyte release.
- The effect of IFN-beta on MMP expression in glial cells remains to be fully elucidated.
Purpose of the Study:
- To investigate the effect of IFN-beta on the expression of MMP-2 and MMP-9 in rat microglial and astrocyte cultures.
- To determine if IFN-beta can modulate MMP release from central nervous system (CNS) cells.
Main Methods:
- Rat microglial and astrocyte cultures were treated with varying doses of IFN-beta.
- Cells were activated with lipopolysaccharide (LPS) either before or simultaneously with IFN-beta treatment.
- Culture supernatants were analyzed for MMP-2 and MMP-9 levels using zymography.
Main Results:
- LPS treatment increased MMP-9 and MMP-2 in astrocyte supernatants and MMP-9 in microglial supernatants.
- IFN-beta dose-dependently inhibited MMP-2 and MMP-9 expression in LPS-stimulated astrocytes.
- IFN-beta also inhibited MMP-9 expression in LPS-stimulated microglia.
Conclusions:
- IFN-beta exhibits a dose-dependent inhibitory effect on MMP release from astrocytes and microglia.
- This modulation of MMPs by IFN-beta offers a potential mechanism for reducing CNS lesion development in MS.
- These findings highlight a novel therapeutic pathway for managing multiple sclerosis progression.
