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Inhibitory effect of polyunsaturated fatty acids on MMP-9 release from microglial cells--implications for
Grazia Maria Liuzzi1, Tiziana Latronico, Rocco Rossano
1Department of Biochemistry and Molecular Biology, University of Bari, Bari, Italy.
Abstract:
We investigated whether polyunsaturated fatty acids (PUFA), which might be a useful complementary therapy among patients with multiple sclerosis (MS), are able to modulate matrix metalloproteinase (MMP) production in microglial cultures. MMPs are myelinotoxic factors. Primary cultures of rat microglia were treated with different doses of omega-3 (omega-3) PUFA or purified fish oil, containing a mixture of omega-3 and omega-6 PUFA, and simultaneously activated by exposure to lipopolysaccharide (LPS). Culture supernatants were subjected to zymography and Western blot analysis for the assessment of MMP-2 and MMP-9 levels. Increased amounts of MMP-9, but not of the constitutively expressed MMP-2, were observed in supernatants from LPS-treated microglia in comparison with non-treated control cells. The treatment with both omega-3 PUFA and fish oil dose-dependently inhibited the LPS-induced production of MMP-9. Our results suggest that a low fat diet supplemented with omega-3 PUFA may become recommended for the well being of MS patients under therapy.
Insights
Polyunsaturated fatty acids (PUFA) can inhibit matrix metalloproteinase-9 (MMP-9) production in microglial cells. This finding suggests omega-3 PUFA supplementation may benefit multiple sclerosis patients by reducing myelinotoxic factors.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Multiple sclerosis (MS) involves myelin damage, and matrix metalloproteinases (MMPs) are implicated as myelinotoxic factors.
- Polyunsaturated fatty acids (PUFA) are being explored as potential complementary therapies for MS patients.
Purpose of the Study:
- To investigate the effect of omega-3 PUFA on matrix metalloproteinase (MMP) production in microglial cells.
- To determine if PUFA can modulate MMP-2 and MMP-9 levels, which are associated with myelin degradation.
Main Methods:
- Primary rat microglial cultures were treated with varying doses of omega-3 PUFA or fish oil.
- Cells were activated with lipopolysaccharide (LPS) and analyzed for MMP-2 and MMP-9 levels using zymography and Western blot.
Main Results:
- LPS-activated microglia showed increased MMP-9 production compared to controls.
- Neither omega-3 PUFA nor fish oil affected constitutive MMP-2 levels.
- Both omega-3 PUFA and fish oil treatments dose-dependently inhibited LPS-induced MMP-9 production.
Conclusions:
- Omega-3 PUFA effectively inhibits the production of MMP-9 in activated microglial cells.
- These findings support the potential therapeutic role of omega-3 PUFA supplementation in managing multiple sclerosis.