Kupffer cells suppress perfluorononanoic acid-induced hepatic peroxisome proliferator-activated receptor α expression by releasing cytokines
Fang, X; Zou, S; Zhao, Y; Cui, R; Zhang, W; Hu, J; Dai, J
HERO ID
3054217
Reference Type
Journal Article
Year
2012
Language
English
PMID
| HERO ID | 3054217 |
|---|---|
| In Press | No |
| Year | 2012 |
| Title | Kupffer cells suppress perfluorononanoic acid-induced hepatic peroxisome proliferator-activated receptor α expression by releasing cytokines |
| Authors | Fang, X; Zou, S; Zhao, Y; Cui, R; Zhang, W; Hu, J; Dai, J |
| Journal | Archives of Toxicology |
| Volume | 86 |
| Issue | 10 |
| Page Numbers | 1515-1525 |
| Abstract | Kupffer cells (KCs) have been demonstrated to play a role in the regulation of intra-hepatic lipid metabolism through the synthesis and secretion of biologically active products. The involvement of KCs in the disturbance of lipid metabolism that induced by perfluorononanoic acid (PFNA), a known agonist of the peroxisome proliferator-activated receptor alpha (PPARα), was investigated in this study. Rats were exposed to PFNA or PFNA combined with gadolinium chloride, an inhibitor of KCs, for 14 days. PFNA exposure dose-dependently increased absolute and relative liver weights, induced triglyceride accumulation, up-regulated the expression of both SERBP-1c and PPARα, and stimulated the release of TNFα and IL-1β. Inactivation of KCs markedly lowered TNFα and IL-1β level, enhanced PFNA-induced expression of PPARα and its target genes, and reduced liver triglyceride levels. In vitro, PFNA-induced expression of PPARα in primary cultured hepatocytes was suppressed by recombinant rat TNFα and IL-1β. However, inhibition of the NF-κB pathway prevented this. Transient transfection and promoter analysis further revealed that these two cytokines and NF-κB were coordinately involved in the suppression of PPARα promoter activity. Our data demonstrate that TNFα and IL-1β released from KCs following PFNA exposure can suppress the expression of PPARα via NF-κB pathway, which partially contribute to the evident accumulation of triglycerides in rat liver. |
| Doi | 10.1007/s00204-012-0877-4 |
| Pmid | 22648072 |
| Wosid | WOS:000308640500004 |
| Url | https://search.proquest.com/docview/1038912629?accountid=171501 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Keyword | Peroxisome proliferator-activated receptors; NF-kappa B; Lipid metabolism; Hepatotoxicity; Perfluorinated compound |