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  • Title: Eicosapentaenoic acid inhibits TNF-alpha-induced matrix metalloproteinase-9 expression in human keratinocytes, HaCaT cells.
    Author: Kim HH, Lee Y, Eun HC, Chung JH.
    Journal: Biochem Biophys Res Commun; 2008 Apr 04; 368(2):343-9. PubMed ID: 18222174.
    Abstract:
    Eicosapentaenoic acid (EPA) is an omega-3 (omega-3) polyunsaturated fatty acid (PUFA), which has anti-inflammatory and anti-cancer properties. Some reports have demonstrated that EPA inhibits NF-kappaB activation induced by tumor necrosis factor (TNF)-alpha or lipopolysaccharide (LPS) in various cells. However, its detailed mode of action is unclear. In this report, we investigated whether EPA inhibits the expression of TNF-alpha-induced matrix metalloproteinases (MMP)-9 in human immortalized keratinocytes (HaCaT). TNF-alpha induced MMP-9 expression by NF-kappaB-dependent pathway. Pretreatment of EPA inhibited TNF-alpha-induced MMP-9 expression and p65 phosphorylation. However, EPA could not affect IkappaB-alpha phosphorylation, nuclear translocation of p65, and DNA binding activity of NF-kappaB. EPA inhibited TNF-alpha-induced p65 phosphorylation through p38 and Akt inhibition and this inhibition was IKKalpha-dependent event. Taken together, we demonstrate that EPA inhibits TNF-alpha-induced MMP-9 expression through inhibition of p38 and Akt activation.
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