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Arachidonic acid increases matrix metalloproteinase 9 secretion and expression in human monocytic MonoMac 6 cells.

Solakivi T, Kunnas T, Kärkkäinen S, Jaakkola O, Nikkari ST - Lipids Health Dis (2009)

Bottom Line: Supplementation with AA (but not the n-3 fatty acids) increased, in a dose-dependent manner, expression of MMP-9 protein.MMP-9 secretion started after 1 h of incubation and could not be prevented by simultaneous presence of n-3 series fatty acids.Finally, the secretion could be attenuated by LY 294002, a specific phosphatidylinositol-3-kinase (PI3K) inhibitor and by SH-5, a selective Akt inhibitor, suggesting that activation of PI3K by AA leads to augmented and sustained MMP-9 production.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medical Biochemistry, University of Tampere Medical School, Finland. tiina.solakivi@uta.fi

ABSTRACT

Background: Dietary fatty acids may modulate inflammation in macrophages of the atherosclerotic plaque, affecting its stability. The n-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA) generally promotes inflammation, while the PUFAs of the n-3 series eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) are considered anti-inflammatory. We determined how these PUFAs influence MMP-9 expression and secretion by the human monocytic cell line (MonoMac 6) at baseline and after 24-hour exposure. MMP-9 protein was measured by zymography and relative levels of MMP-9 mRNA were determined using quantitative real time PCR.

Results: Supplementation with AA (but not the n-3 fatty acids) increased, in a dose-dependent manner, expression of MMP-9 protein. This stimulation was regulated at the mRNA level. MMP-9 secretion started after 1 h of incubation and could not be prevented by simultaneous presence of n-3 series fatty acids. Finally, the secretion could be attenuated by LY 294002, a specific phosphatidylinositol-3-kinase (PI3K) inhibitor and by SH-5, a selective Akt inhibitor, suggesting that activation of PI3K by AA leads to augmented and sustained MMP-9 production.

Conclusion: This study shows that of the PUFA studied, AA alone influences the expression of MMP-9, which might have implications in MMP-9 induced plaque rupture.

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Related in: MedlinePlus

Effect of docosapentaenoic acid (DPA) on arachidonic acid (AA) stimulated production of MMP-9. MonoMac 6 cells (0.8 × 106 cells/ml in X-Vivo 15) were incubated in the presence of 5 μM arachidonic acid and increasing concentrations of DPA (1, 5, 10 μM) for 24 h. The presence of MMP-9 activity in the media was determined using zymography.
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Figure 3: Effect of docosapentaenoic acid (DPA) on arachidonic acid (AA) stimulated production of MMP-9. MonoMac 6 cells (0.8 × 106 cells/ml in X-Vivo 15) were incubated in the presence of 5 μM arachidonic acid and increasing concentrations of DPA (1, 5, 10 μM) for 24 h. The presence of MMP-9 activity in the media was determined using zymography.

Mentions: Since EPA, DPA or DHA by themselves had no effect on MMP-9 secretion, we looked at their effect on AA-induced production of MMP-9. Co-incubation of 5 μM AA with increasing concentrations of EPA, DPA or DHA for 24 h did not diminish or increase the secretion of MMP-9 (Fig. 3).


Arachidonic acid increases matrix metalloproteinase 9 secretion and expression in human monocytic MonoMac 6 cells.

Solakivi T, Kunnas T, Kärkkäinen S, Jaakkola O, Nikkari ST - Lipids Health Dis (2009)

Effect of docosapentaenoic acid (DPA) on arachidonic acid (AA) stimulated production of MMP-9. MonoMac 6 cells (0.8 × 106 cells/ml in X-Vivo 15) were incubated in the presence of 5 μM arachidonic acid and increasing concentrations of DPA (1, 5, 10 μM) for 24 h. The presence of MMP-9 activity in the media was determined using zymography.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2667508&req=5

Figure 3: Effect of docosapentaenoic acid (DPA) on arachidonic acid (AA) stimulated production of MMP-9. MonoMac 6 cells (0.8 × 106 cells/ml in X-Vivo 15) were incubated in the presence of 5 μM arachidonic acid and increasing concentrations of DPA (1, 5, 10 μM) for 24 h. The presence of MMP-9 activity in the media was determined using zymography.
Mentions: Since EPA, DPA or DHA by themselves had no effect on MMP-9 secretion, we looked at their effect on AA-induced production of MMP-9. Co-incubation of 5 μM AA with increasing concentrations of EPA, DPA or DHA for 24 h did not diminish or increase the secretion of MMP-9 (Fig. 3).

Bottom Line: Supplementation with AA (but not the n-3 fatty acids) increased, in a dose-dependent manner, expression of MMP-9 protein.MMP-9 secretion started after 1 h of incubation and could not be prevented by simultaneous presence of n-3 series fatty acids.Finally, the secretion could be attenuated by LY 294002, a specific phosphatidylinositol-3-kinase (PI3K) inhibitor and by SH-5, a selective Akt inhibitor, suggesting that activation of PI3K by AA leads to augmented and sustained MMP-9 production.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medical Biochemistry, University of Tampere Medical School, Finland. tiina.solakivi@uta.fi

ABSTRACT

Background: Dietary fatty acids may modulate inflammation in macrophages of the atherosclerotic plaque, affecting its stability. The n-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA) generally promotes inflammation, while the PUFAs of the n-3 series eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) are considered anti-inflammatory. We determined how these PUFAs influence MMP-9 expression and secretion by the human monocytic cell line (MonoMac 6) at baseline and after 24-hour exposure. MMP-9 protein was measured by zymography and relative levels of MMP-9 mRNA were determined using quantitative real time PCR.

Results: Supplementation with AA (but not the n-3 fatty acids) increased, in a dose-dependent manner, expression of MMP-9 protein. This stimulation was regulated at the mRNA level. MMP-9 secretion started after 1 h of incubation and could not be prevented by simultaneous presence of n-3 series fatty acids. Finally, the secretion could be attenuated by LY 294002, a specific phosphatidylinositol-3-kinase (PI3K) inhibitor and by SH-5, a selective Akt inhibitor, suggesting that activation of PI3K by AA leads to augmented and sustained MMP-9 production.

Conclusion: This study shows that of the PUFA studied, AA alone influences the expression of MMP-9, which might have implications in MMP-9 induced plaque rupture.

Show MeSH
Related in: MedlinePlus