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学科主题: 基础医学
题名:
ROS and NF-kappa B but not LXR mediate IL-1 beta signaling for the downregulation of ATP-binding cassette transporter A1
作者: Chen, Min1; Li, Wenjing1; Wang, Nanping1; Zhu, Yi1; Wang, Xian1
关键词: interleukin-1 beta ; nuclear factor-kappa B ; reactive oxygen species
刊名: AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
发表日期: 2007-04-01
DOI: 10.1152/ajpcell.00016.2006
卷: 292, 期:4, 页:C1493-C1501
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell Biology ; Physiology
研究领域[WOS]: Cell Biology ; Physiology
关键词[WOS]: LIVER-X-RECEPTOR ; CELLULAR CHOLESTEROL EFFLUX ; HIGH-DENSITY-LIPOPROTEIN ; RECIPROCAL REGULATION ; TRANSCRIPTION FACTOR ; LIPID-METABOLISM ; GENE-EXPRESSION ; PEST SEQUENCE ; APOA-I ; ABCA1
英文摘要:

ATP- binding cassette transporter A1 ( ABCA1), a pivotal regulator of cholesterol efflux from cells to apolipoproteins, plays an important role in cholesterol homeostasis. As an inflammatory factor, IL-1 beta has been shown to downregulate ABCA1 in macrophages and facilitates foam cell formation. However, the molecular mechanism underlining the downregulated ABCA1 by IL-1 beta is still elusive. In the present study, we demonstrated that IL-1 beta downregulated ABCA1 but not ABCG1 at mRNA and protein levels in a time- and dose- dependent manner in THP- 1 and A549 cells. IL-1 beta attenuated ABCA1 promoter activity through an LXR ( liver X receptor)- independent pathway, since IL-1 beta did not alter the expression and activities of LXR alpha/beta, and deletion of the LXR responsive element from the ABCA1 promoter failed to reverse the IL-1 beta effect. In contrast, NF-kappa B inhibition by pyrrolidine dithiocarbamate and MG132 prevented the suppression of ABCA1 by IL-1 beta. Cotransfection with ABCA1 luciferase reporter and the expression plasmids of Rel A decreased ABCA1 promoter activities. An adenovirus expressing NF-kappa B inhibitor subunit-alpha inhibited NF-kappa B activities and also reversed the IL-1 beta effect at the promoter activity and protein levels of ABCA1. In addition, IL-1 beta could induce the production of reactive oxygen species ( ROS), and N- acetyl- L- cysteine, a scavenger of ROS, reversed the decreased level of ABCA1 induced by IL-1 beta. H2O2 decreased ABCA1 at the mRNA and protein levels and the promoter activity. Thus our data provide strong evidence that ROS and NF-kappa B, but not LXR, mediate the IL-1 beta- induced downregulation of ABCA1 via a novel transcriptional mechanism, which might play an important role of proinflammation in the alteration of lipid metabolism.

语种: 英语
WOS记录号: WOS:000247936400032
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52787
Appears in Collections:基础医学院_期刊论文

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作者单位: 1.Peking Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Beijing 100083, Peoples R China
2.Peking Univ, Key Lab Mol Cardiovasc Sci, Minist Educ, Beijing 100083, Peoples R China

Recommended Citation:
Chen, Min,Li, Wenjing,Wang, Nanping,et al. ROS and NF-kappa B but not LXR mediate IL-1 beta signaling for the downregulation of ATP-binding cassette transporter A1[J]. AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY,2007,292(4):C1493-C1501.
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