Prostaglandin-J2 induces synthesis of interleukin-8 by endothelial cells in a PPARγ-independent manner

被引:52
作者
Jozkowicz, A
Dulak, J
Prager, M
Nanobashvili, J
Nigisch, A
Winter, B
Weigel, G
Huk, I
机构
[1] Univ Vienna, Dept Vasc Surg, AKH, Vienna, Austria
[2] Jagiellonian Univ, Dept Clin Biochem, Collegium Medicum, Krakow, Poland
[3] Univ Innsbruck, Div Cardiol, A-6020 Innsbruck, Austria
[4] Univ Vienna, AKH, Dept Cardiothorac Surg, Vienna, Austria
关键词
D O I
10.1016/S0090-6980(01)00155-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
PPAR gamma is a transcription factor of nuclear receptor superfamily, involved in the regulation of inflammation. We investigated the influence of PPAR gamma -ligands, 15-deoxy-Delta (12,14) prostaglandin-J(2) (15d-PGJ(2)), and ciglitazone, on the generation of interleukin-8 (IL-8) by the human microvascular endothelial cell line (HMEC-1). Expression of PPAR gamma in HMEC-1 was confirmed by RT-PCR. Both PPAR gamma -ligands tested induced the activation of PPAR, but the potency of ciglitazone was higher, as evidenced by luciferase assay. Resting HMEC-1 released about 150 pg/ml of IL-8 protein. Treatment with LPS increased the IL-8 secretion up to 1 ng/ml. 15d-PGJ(2) potently and dose-dependently increased both the steady-state and LPS-induced generation of IL-8 mRNA and IL-8 protein. In contrast, neither basal nor LPS-elicited expression of IL-8 was influenced by ciglitazone. We conclude, that 15d-PGJ(2) is a potent inducer of IL-8 production and can be a mediator of inflammatory response, but this effect is independent of PPAR gamma activation. (C) 2001 Elsevier Science Inc. All rights reserved.
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页码:165 / 177
页数:13
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