Eicosapentaenoic acid inhibits TNF-alpha-induced matrix metalloproteinase-9 expression in human keratinocytes, HaCaT cells.
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.
Kim
Hyeon Ho
HH
Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Lee
Youngae
Y
Eun
Hee Chul
HC
Chung
Jin Ho
JH
D002460:Cell Line; D004347:Drug Interactions; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D015118:Eicosapentaenoic Acid; D020780:Matrix Metalloproteinase 9