7-Ketocholesterol upregulates interleukin-6 via mechanisms that are distinct from those of tumor necrosis factor-alpha, in vascular smooth muscle cells.
J Vasc Res
; 46(1): 36-44, 2009.
Article
in En
| MEDLINE
| ID: mdl-18515973
ABSTRACT
This study investigated the effects of 7-ketocholesterol on interleukin (IL)-6 expression in vascular smooth muscle cells (VSMC). Among the 7 IL examined, only IL-6 transcript was increased by 7-ketocholesterol treatment in human aorta smooth muscle cells. IL-6 transcripts increased up to 24 h after treatment with 7-ketocholesterol, and this effect was profoundly repressed by treatment with p38 MAPK inhibitors and to a lesser extent JNK inhibitors. 7alpha-Hydroxycholesterol, 27-hydroxycholesterol or cholesterol, however, did not induce IL-6 expression. Mechanisms of IL-6 induction by 7-ketocholesterol were investigated in comparison with tumor necrosis factor (TNF)-alpha. Whereas TNF-alpha activated IL-6 promoter, which was impaired by p38 MAPK inhibitors or by mutation in the NF-kappaB-binding site within the promoter region, 7-ketocholesterol did not affect IL-6 promoter activity. Instead, this oxysterol slowed degradation of IL-6 mRNA and increased the amount of cytoplasmic HuR. 7-ketocholesterol significantly increased the amount of intracellular IL-6 protein in the presence of brefeldin A. 7-Ketocholesterol also enhanced IL-6 release from VSMC. IL-6 release by 7-ketocholesterol, although significant, was not as remarkable as that induced by TNF-alpha. These data suggest that 7-ketocholesterol upregulates IL-6 via mechanisms distinct from TNF-alpha and contributes to the intra- and extracellular IL-6 deposits within the vasculature.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Interleukin-6
/
Tumor Necrosis Factor-alpha
/
Ketocholesterols
/
Muscle, Smooth, Vascular
Limits:
Animals
/
Humans
Language:
En
Journal:
J Vasc Res
Journal subject:
ANGIOLOGIA
Year:
2009
Type:
Article