title: Arachidonic acid increases matrix metalloproteinase 9 secretion and expression in human monocytic MonoMac 6 cells.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Biochemistry, University of Tampere Medical School, Finland. tiina.solakivi@uta.fi
authors.forename: Tiina
authors.initials: T
authors.lastname: Solakivi
authors.forename: Tarja
authors.initials: T
authors.lastname: Kunnas
authors.forename: Satu
authors.initials: S
authors.lastname: Kärkkäinen
authors.forename: Olli
authors.initials: O
authors.lastname: Jaakkola
authors.forename: Seppo T
authors.initials: ST
authors.lastname: Nikkari