| TNF-alpha decreases ABCA1 expression and attenuates HDL cholesterol efflux in the human intestinal cell line Caco-2. | |
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MedLine Citation:
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PMID: 20103810 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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HDL cholesterol levels are decreased in Crohn's disease, a tumor necrosis factor-alpha (TNF-alpha)-driven chronic inflammatory condition involving the gastrointestinal tract. ATP-binding cassette transporter A1 (ABCA1), one of several liver X receptor (LXR) target genes, is a cell surface transporter that mediates the rate-controlling step in HDL synthesis. The regulation of ABCA1 and HDL cholesterol efflux by TNF-alpha was investigated in the human intestinal cell line Caco-2. In response to cholesterol micelles or T0901317, an LXR nonsterol agonist, TNF-alpha decreased the basolateral efflux of cholesterol to apolipoprotein A1 (apoA1). TNF-alpha, by attenuating ABCA1 promoter activity, markedly decreased ABCA1 gene expression without attenuating the expression of LXR-alpha, LXR-beta, and most other LXR target genes, such as ABCG1, FAS, ABCG8, scavenger receptor-B1 (SR-B1), and apoC1. TNF-alpha also decreased ABCA1 mass by markedly enhancing the rate of ABCA1 degradation and modestly inhibiting its rate of synthesis. Inhibitors of the nuclear factor-kappaB (NF-kappaB) pathway, which is activated by TNF-alpha, partially reverse the effect of TNF-alpha on ABCA1 protein expression. The results suggest that TNF-alpha, the major cytokine implicated in the inflammation of Crohn's disease, decreases HDL cholesterol levels by attenuating the expression of intestinal ABCA1 and cholesterol efflux to apoA1. |
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Authors:
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F Jeffrey Field; Kim Watt; Satya N Mathur |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-01-26 |
Journal Detail:
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Title: Journal of lipid research Volume: 51 ISSN: 0022-2275 ISO Abbreviation: J. Lipid Res. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-12 Completed Date: 2010-08-17 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 0376606 Medline TA: J Lipid Res Country: United States |
Other Details:
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Languages: eng Pagination: 1407-15 Citation Subset: IM |
Affiliation:
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Department of Internal, Medicine University of Iowa, Iowa City, IA 52242, USA. f-jeffrey-fi eld@uiowa.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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ATP-Binding Cassette Transporters
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genetics* Animals Caco-2 Cells Cholesterol, HDL / metabolism* Gene Expression Regulation / drug effects* Humans Intestines / cytology*, metabolism NF-kappa B / metabolism Orphan Nuclear Receptors / metabolism Signal Transduction / drug effects Tumor Necrosis Factor-alpha / pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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DK-67132/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/ATP binding cassette transporter 1; 0/ATP-Binding Cassette Transporters; 0/Cholesterol, HDL; 0/NF-kappa B; 0/Orphan Nuclear Receptors; 0/Tumor Necrosis Factor-alpha; 0/liver X receptor |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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