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Omega-3 polyunsaturated fatty acids inhibit the release of matrix metalloproteinases: therapeutic implications for HIV-associated immune activation
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IAS Capetown July 19-22 2009
Reported by Jules Levin
G.M. Liuzzi1, L. Tiziana1, A. Fasano1, S. Viggiano2, R. Paolo2, M. Lichtner3, C.M. Mastroianni3
1University of Bari, Bari, Italy, 2University of Potenza, Potenza, Italy, 3Sapienza University, Latina, Italy
Background: A pathologic consequence of the chronic immune activation seen in HIV disease is the excessive activity of matrix metalloproteinases (MMPs) which can facilitate viral dissemination and tissue disruption possibly contributing to the development of neurologic, metabolic and atheroscolerotic disease. Omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) are commonly used for the management of HIV-related dyslipidemia. Animal experiments and clinical intervention studies indicate that ω-3 PUFAs have immunomodulatory and anti-inflammatory properties.
Methods: Primary cultures of rat microglia were treated with different doses of ω-3 PUFA or purified fish oil, containing a mixture of ω-3 and ω-6 PUFA, and simultaneously activated by exposure to LPS. Culture supernatants were subjected to zymography and Western blot analysis for the assessment of MMP-2 and MMP-9 levels.
Results: 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 of microglia with ω-3 PUFA or with fish oil dose-dependently inhibited the amounts of MMP-9 produced by LPS-activated microglia, but not the levels of MMP-2, which was constitutively expressed. The inhibition of MMP-9 was more evident in cells treated with ω-3 rather than fish oil. The strongest inhibition of MMP-9 activity was reached at the concentration of 200 mg/ml for ω-3 and 740 mg/ml for fish oil, corresponding to 200 mg/ml of ω-3. In addition, we performed a set of experiments using Western blot analysis to detect protein expression of MMP-2 and MMP-9. The results showed that PUFA only exert an
inhibitory effect on the protein expression of MMP-9 but not of MMP-2.
Conclusions: The administration of ω-3 PUFAs in HIV-infected individuals might be useful not only for the management of metabolic disorders, but also to combat the host detrimental effect of chronic inflammation and exaggerated MMP activity in neurologic and atherosclerotic diseases.
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