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Eicosapentaenoic acid inhibits TNF-alpha-induced matrix metalloproteinase-9 expression in human keratinocytes, HaCaT cells |
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| Authors: | Kim Hyeon Ho Lee Youngae Eun Hee Chul Chung Jin Ho |
| Institution: | a Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea b Laboratory of Cutaneous Aging Research, Department of Dermatology, Clinical Research Institutes, Seoul National University Hospital, 28 Yongon-dong, Jongno-gu, Seoul 110-744, Republic of Korea c Institute of Dermatological Science, Seoul National University, Seoul, Republic of Korea |
| Abstract: | Eicosapentaenoic acid (EPA) is an omega-3 (ω-3) polyunsaturated fatty acid (PUFA), which has anti-inflammatory and anti-cancer properties. Some reports have demonstrated that EPA inhibits NF-κB activation induced by tumor necrosis factor (TNF)-α 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-α-induced matrix metalloproteinases (MMP)-9 in human immortalized keratinocytes (HaCaT). TNF-α induced MMP-9 expression by NF-κB-dependent pathway. Pretreatment of EPA inhibited TNF-α-induced MMP-9 expression and p65 phosphorylation. However, EPA could not affect IκB-α phosphorylation, nuclear translocation of p65, and DNA binding activity of NF-κB. EPA inhibited TNF-α-induced p65 phosphorylation through p38 and Akt inhibition and this inhibition was IKKα-dependent event. Taken together, we demonstrate that EPA inhibits TNF-α-induced MMP-9 expression through inhibition of p38 and Akt activation. |
| Keywords: | EPA eicosapentaenoic acid PUFA polyunsaturated fatty acid TNF-α tumor necrosis factor-alpha MMP-9 matrix metalloproteinases-9 NF-κB nuclear factor kappa B IκB-α inhibitory subunit of NF-κB IKK IκB-α kinase |
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