サイトクロームP450エポキシゲネーゼ由来イコサノイドの抗炎症性
1Vascular Medicine and Atherosclerosis Unit, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Avenue, LMRC-322, Boston, MA 02115, USA.
Science (New York, N.Y.)
|August 24, 1999
まとめ
サイトクロームP450エポキシゲナーゼによって生成されるエポキシエコサトリエノ酸 (EETs) は,白血球の粘着を抑制することにより,血管の炎症を軽減します. これらの効果は血管拡張性とは無関係であり,血管の健康における重要な非血管拡張性作用を強調しています.
科学分野:
- バイオケミストリー バイオケミストリー
- 分子生物学は分子生物学である.
- 血管生物学 血管生物学
背景:
- エポキシエコサトリエノ酸 (EET) は,サイトクロームP450 (CYP) エポキシゲナーゼによって生成される血管活性代謝産物である.
- EETは,内皮に由来するハイパーポラライジングファクターを模倣し,血管トーンを調節する役割を示唆しています.
- ヒト内皮細胞におけるEET生成を司る特定のCYPイソフォームが調査されました.
研究 の 目的:
- ヒト内皮細胞におけるEET生成に責任を負うCYPイソフォームを特定する.
- 内皮細胞の粘着分子の発現を調節するEETの役割を調査する.
- EETが白血球の血管壁への粘着に影響を与えるメカニズムを解明する.
主な方法:
- 人間のCYP2J2イソフォームのクローン化.
- 内皮細胞をEETまたはCYP2J2の過剰発現で治療する2.
- サイトカイン誘発の内皮細胞粘着分子発現の評価.
- 血管壁に対する白血球の粘着の分析.
- NF-kappaBとIkappaBキナーゼシグナル伝達経路の関与の調査.
主要な成果:
- サイトクロームP450イソフォームCYP2J2は,ヒト内皮細胞におけるEETの源として特定されました.
- EETsの生理学的濃度またはCYP2J2過剰発現は,サイトカイン誘発の内皮細胞粘着分子発現を減少させます.
- EETは白血球の血管壁への粘着を阻害した.
- 抑制メカニズムは,転写因子NF-kappaBとIkappaBキナーゼの抑制を伴う.
- EETのこれらの抗炎症効果は,その膜をハイパーポラライズする性質とは無関係であった.
結論:
- CYP2J2は,ヒト内皮細胞におけるEETの重要な源である.
- EETは,内皮細胞の活性化と白血球の粘着を抑制することによって強力な抗炎症効果を発揮します.
- EETは,血管拡張作用とは独立して,血管の炎症を調節する上で,血管拡張作用以外の重要な役割を果たします.
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