RU486 antagonizes the inhibitory effect of peroxisome proliferator-activated receptor α on interleukin-6 production in vascular endothelial cells

Autor: Haruhiko Kouhara, Soji Kasayama, Michio Otsuki, Xin Xu, Hiroshi Saito, Satoru Sumitani
Rok vydání: 2002
Předmět:
medicine.medical_specialty
Vascular smooth muscle
Endocrinology
Diabetes and Metabolism
medicine.medical_treatment
Clinical Biochemistry
Receptors
Cytoplasmic and Nuclear
Peroxisome proliferator-activated receptor
Biology
digestive system
Biochemistry
Endocrinology
Fenofibrate
Internal medicine
medicine
Animals
Humans
Fluorescent Antibody Technique
Indirect
Receptor
Molecular Biology
Cells
Cultured
Cell Nucleus
chemistry.chemical_classification
Interleukin-6
Tumor Necrosis Factor-alpha
Activator (genetics)
nutritional and metabolic diseases
Cell Biology
Cell biology
Endothelial stem cell
Mifepristone
Protein Transport
Cytokine
Nuclear receptor
chemistry
cardiovascular system
Molecular Medicine
Cattle
lipids (amino acids
peptides
and proteins)
Tumor necrosis factor alpha
Endothelium
Vascular
Transcription Factors
Zdroj: The Journal of Steroid Biochemistry and Molecular Biology. 81:141-146
ISSN: 0960-0760
Popis: Peroxisome proliferator-acitivated receptor alpha (PPARalpha) is a member of nuclear receptor superfamily. Recent studies have shown that the activators for PPARalpha inhibit the expression of some inflammatory molecules in vascular endothelial cells (ECs) and vascular smooth muscle cells, indicating the anti-inflammatory roles of PPARalpha on vascular walls. In this investigation, we showed that RU486, already proved to be an active anti-glucocorticoid and anti-progesterone agent, blocked the inhibition of tumor necrosis factor (TNF)-alpha-stimulated interleukin-6 (IL-6) production by the PPARalpha activator fenofibrate in human umbilical vein ECs. Transient transfection of bovine aortic ECs with an IL-6 promoter construct demonstrated that RU486 blocked the inhibitory effect of fenofibrate on TNF-alpha-induced IL-6 promoter activity. By fluorescence microscopy, RU486 was found to prevent fenofibrate-induced nuclear translocation of PPARalpha. Thus, RU486 has an antagonizing effect on PPARalpha-mediated down-regulation of IL-6 in vascular ECs. This effect may be exerted by its interference with the nuclear translocation of PPARalpha.
Databáze: OpenAIRE
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