| Dysregulation of LDL receptor under the influence of inflammatory cytokines: a new pathway for foam cell formation. | |
| | |
MedLine Citation:
|
PMID: 11703589 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND: Lipid-mediated renal injury is an important component of glomerulosclerosis and its similarity to atherosclerosis is well described. This study focused on the relationship between lipid-mediated injury and inflammation by examining the role of inflammatory cytokines in the regulation of human mesangial cell low-density lipoprotein (LDL) receptors. METHODS: A human mesangial cell line (HMCL) was used to study the effects of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) on the regulation of LDL receptor mRNA and protein in the presence of a high concentration of native LDL (250 microg/mL). RESULTS: Native LDL caused foam cell formation in HMCL in the presence of antioxidants, TNF-alpha and IL-1beta. Both cytokines overrode LDL receptor suppression induced by a high concentration of LDL and increased LDL uptake by enhancing receptor expression. These cytokines also caused increased expression of SCAP [sterol responsive element binding protein (SREBP) cleavage activation protein], and an increase in the nuclear translocation of SREBP, which induces LDL receptor expression. CONCLUSION: These observations demonstrate that inflammatory cytokines can modify cholesterol-mediated LDL receptor regulation in mesangial cells, permitting unregulated intracellular accumulation of unmodified LDL and causing foam cell formation. These findings suggest that inflammatory cytokines contribute to lipid-mediated renal damage, and also may have wider implications for the study of inflammation in the atherosclerotic process. |
| | |
Authors:
|
X Z Ruan; Z Varghese; S H Powis; J F Moorhead |
Related Documents
:
|
17395779 - Bovine apolipoprotein b-100 is a dominant immunogen in therapeutic cell populations cul... 3861749 - Monocytes and neutrophils oxidize low density lipoprotein making it cytotoxic. 3280179 - Immunohistochemical demonstration of migration inhibitory factor (mif) in experimental ... 17621699 - The role of macrophage migration inhibitory factor in maintaining the immune privilege ... 18439909 - Macrophage migration inhibitory factor induces cardiomyocyte apoptosis. 9006339 - Migration inhibitory factor expression in experimentally induced endotoxemia. 16113289 - Components of the legionella pneumophila flagellar regulon contribute to multiple virul... 20107539 - Cordycepin suppresses expression of diabetes regulating genes by inhibition of lipopoly... 15261489 - The role of calcium in hypoxia-induced signal transduction and gene expression. |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: Kidney international Volume: 60 ISSN: 0085-2538 ISO Abbreviation: Kidney Int. Publication Date: 2001 Nov |
Date Detail:
|
Created Date: 2001-11-12 Completed Date: 2002-01-10 Revised Date: 2006-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 0323470 Medline TA: Kidney Int Country: United States |
Other Details:
|
Languages: eng Pagination: 1716-25 Citation Subset: IM |
Affiliation:
|
Centre for Nephrology, Royal Free and University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, England, UK. xzruan@rfc.ucl.ac.uk |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
CCAAT-Enhancer-Binding Proteins
/
genetics Cells, Cultured DNA-Binding Proteins / genetics Foam Cells / physiology* Gene Expression Regulation / drug effects* Glomerular Mesangium / cytology, drug effects* Humans Interleukin-1 / pharmacology* Intracellular Signaling Peptides and Proteins Membrane Proteins / genetics RNA, Messenger / analysis Receptors, LDL / drug effects*, genetics Sterol Regulatory Element Binding Protein 1 Transcription Factors* Tumor Necrosis Factor-alpha / pharmacology* |
| Chemical | |
Reg. No./Substance:
|
0/CCAAT-Enhancer-Binding Proteins; 0/DNA-Binding Proteins; 0/Interleukin-1; 0/Intracellular Signaling Peptides and Proteins; 0/Membrane Proteins; 0/RNA, Messenger; 0/Receptors, LDL; 0/SREBF1 protein, human; 0/SREBP cleavage-activating protein; 0/Sterol Regulatory Element Binding Protein 1; 0/Transcription Factors; 0/Tumor Necrosis Factor-alpha |
| Comments/Corrections | |
Comment In:
|
Kidney Int. 2001 Nov;60(5):2037-8
[PMID:
11703627
]
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Pressure-induced expression of monocyte chemoattractant protein-1 through activation of MAP kinase.
Next Document: Role and regulation of activation of caspases in cisplatin-induced injury to renal tubular epithelia...