Journal Article

Lysophosphatidylcholine promotes SREBP-2 activation via rapid cholesterol efflux and SREBP-2-independent cytokine release in human endothelial cells

Mayuko Morita, Azusa Sekine, Yasuomi Urano, Taki Nishimura, Wakako Takabe, Hiroyuki Arai, Takao Hamakubo, Tatsuhiko Kodama and Noriko Noguchi

in The Journal of Biochemistry

Published on behalf of The Japanese Biochemical Society

Volume 158, issue 4, pages 331-338
Published in print October 2015 | ISSN: 0021-924X
Published online May 2015 | e-ISSN: 1756-2651 | DOI: http://dx.doi.org/10.1093/jb/mvv044
Lysophosphatidylcholine promotes SREBP-2 activation via rapid cholesterol efflux and SREBP-2-independent cytokine release in human endothelial cells

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Lysophosphatidylcholine (LPC) and oxysterols which are major components in oxidized low-density lipoprotein have been shown to possess an opposite effect on the expression of sterol regulatory element-binding protein-2 (SREBP-2) target genes in endothelial cells. In this study, we aimed at elucidating the mechanisms of activation of SREBP-2 by LPC and evaluating the effects of LPC and 25-hydroxycholesterol (25-HC) on the release of inflammatory cytokines. Human umbilical vein endothelial cells were treated with LPC or oxysterols including 25-HC. LPC activated SREBP-2 within 15 min, resulting in induction of expression of SREBP-2 target genes which were involved in intracellular cholesterol homeostasis. The rapid activation of SREBP-2 was caused by enhanced efflux of intracellular cholesterol, which was evaluated using 14C-acetate. The LPC-induced activation of SREBP-2 was inhibited by addition of 25-HC. In contrast, both LPC and 25-HC increased release of interleukin-6 (IL-6) and IL-8, respectively and additively. In conclusion, LPC activated SREBP-2 via enhancement of cholesterol efflux, which was suppressed by 25-HC. The release of inflammatory cytokines such as IL-6 and IL-8 in endothelial cells was SREBP-2-independent. LPC and 25-HC may act competitively in cholesterol homeostasis but additively in inflammatory cytokine release.

Keywords: cholesterol; cytokine; 25-hydroxycholesterol; lysophosphatidylcholine; SREBP

Journal Article.  4920 words.  Illustrated.

Subjects: Biochemistry

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