Dysregulation of LDL receptor under the influence of inflammatory cytokines: a new pathway for foam cell formation.
Kidney Int
; 60(5): 1716-25, 2001 Nov.
Article
en En
| MEDLINE
| ID: mdl-11703589
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Receptores de LDL
/
Regulación de la Expresión Génica
/
Interleucina-1
/
Factor de Necrosis Tumoral alfa
/
Células Espumosas
/
Mesangio Glomerular
Límite:
Humans
Idioma:
En
Revista:
Kidney Int
Año:
2001
Tipo del documento:
Article
Pais de publicación:
Estados Unidos