Ceramide induction of COX-2 and PGE2 in pulmonary A549 cells does not involve activation of NF-κB

被引:34
|
作者
Newton, R [1 ]
Hart, L [1 ]
Chung, KF [1 ]
Barnes, PJ [1 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Dept Thorac Med, London SW3 6LY, England
基金
英国医学研究理事会; 英国惠康基金;
关键词
ceramide; sphingomyelinase; cyclooxygenase; prostaglandin; epithelial cell; nuclear factor-kappa B;
D O I
10.1006/bbrc.2000.3722
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
Ceramide is generated by the hydrolysis of membrane sphingomyelin by sphingomyelinase (SMase) and is implicated in multiple signaling pathways, including activation of NF-kappaB. As NF-kappaB is pivotal in the expression of numerous genes associated with airway inflammation and asthma, the effects of ceramide and SMase were examined in human pulmonary A549 cells. Ceramide and SMaase both induced cyclooxygenase (COX)-2 protein expression and stimulated BOB, release. However, neither ceramide nor SMase induced NF-KB DNA-binding, loss of I kappaB alpha, or NF-kappaB-dependent transcription. Both ceramide and SMase were efficient inducers of the extracellular regulated kinase (ERK), but not Jun N-terminal kinase (JNK) or p38 mitogen-activated protein kinase, Since ERK is implicated in arachidonic acid availability, these data partly explain the ability of ceramide to induce PGE(2) release. However, as ERK is not required for IL-1 beta -dependent induction of COX-2, the mechanism of ceramide and SMase induction of COX-2 remains unclear. (C) 2000 Academic Press.
引用
收藏
页码:675 / 679
页数:5
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