@ ↓COX・2含
Ligands ← ABCAl
lCP・1
→
査P臥Rα
←
Macrophage PPARγ
図11:マクロファージにおける、酸化LDLによるPPARs活性化機序の模式図
マクロファージに酸化LDLが作用すると、酸化LDL中の9-HODE、13-HODE、酸化リン脂質がPPARの
直接的なリガンドとなりPPARα、 PPARγを活性化する。一方で、酸化LDLはERKI/2を介した、 COX-2 の過剰発現を誘導し、COX-2の過剰発現が細胞内15d-PGJ2を増加させ、 PPARα、 PPARγの活性化を誘導 する。PPARα、 PPARγの活性化はABCAIのmRNA発現を増加し、 MCP-1のmRNA発現を抑制する。
AA : arachidonic acict ABCAI : ArlP-bindmg cassette transporter Al, COX-2 : cycloxygenase-2,
15d-PGJ2 : 15-deoxy-A’2’i4-prostaglandm J2, ERKI/2 : extracellular・一signal regulated kinase 1/2,
HODE : hydroxyoctadecadienoic acid, Ox-LDL : oxidized low-density lipoprotein,
PPAR : peroxisome proliferator-activated receptor
57
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