Document Detail

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    
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.
X Z Ruan; Z Varghese; S H Powis; J F Moorhead
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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    
Centre for Nephrology, Royal Free and University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, England, UK.
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MeSH Terms
CCAAT-Enhancer-Binding Proteins / genetics
Cells, Cultured
DNA-Binding Proteins / genetics
Foam Cells / physiology*
Gene Expression Regulation / drug effects*
Glomerular Mesangium / cytology,  drug effects*
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*
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
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

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