Related Experiment Video
Updated: Jul 18, 2026
Isolation and Differentiation of Stromal Vascular Cells to Beige/Brite Cells
Published on: March 28, 2013
Rosiglitazone attenuates suppression of RXRalpha-dependent gene expression in inflamed liver
Romi Ghose1, Jaap Mulder, Richard J von Furstenberg
1Texas Children's Liver Center/Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Background/Aims:
A recently determined target of lipopolysaccharide (LPS) and cytokine signaling in liver is the central Type II nuclear receptor (NR) heterodimer partner, retinoid X receptor alpha (RXRalpha). We sought to determine if Rosiglitazone (Rosi), a peroxisome proliferator activated receptor gamma (PPARgamma) agonist with anti-inflammatory properties, can attenuate LPS and cytokine-induced molecular suppression of RXRalpha-regulated genes.
Methods:
In vivo, mice were gavage-fed Rosi for 3 days, prior to intraperitoneal injection of LPS, followed by harvest of liver and serum. In vitro, HepG2 cells were treated with IL-1beta, +/- short-term Rosi pretreatment. RNA was analyzed by quantitative RT-PCR, while nuclear and cytoplasmic proteins were analyzed by immunoblotting and gel shifts.
Results:
Rosi attenuated LPS-mediated suppression of RNA levels of several Type II NR-regulated genes, including bile acid transporters and the major drug metabolizing enzyme, Cyp3a11, without affecting cytokine expression, suggesting a novel, direct anti-inflammatory effect in hepatocytes. Rosi suppressed the inflammation-induced nuclear export of RXRalpha, in both LPS-injected mice and IL-1beta-treated HepG2 cells, leading to maintenance of nuclear RXRalpha levels and heterodimer binding activity.
Conclusions:
Rosi directly attenuates the suppressive effects of inflammation-induced cell signaling on nuclear RXRalpha levels in liver.
Insights
Rosiglitazone (Rosi) prevents inflammation from reducing retinoid X receptor alpha (RXRalpha) levels in liver cells. This drug directly counters inflammation
Area of Science:
- Hepatology
- Molecular Biology
- Pharmacology
Background:
- Lipopolysaccharide (LPS) and cytokine signaling target retinoid X receptor alpha (RXRalpha) in the liver.
- RXRalpha is a key component of Type II nuclear receptor heterodimers.
Purpose of the Study:
- To investigate if Rosiglitazone (Rosi), a PPARgamma agonist, can prevent LPS and cytokine-induced suppression of RXRalpha-regulated genes.
- To determine the direct anti-inflammatory effects of Rosi on liver cells.
Main Methods:
- In vivo studies: Mice treated with Rosi before LPS injection, followed by liver and serum analysis.
- In vitro studies: HepG2 cells treated with IL-1beta and Rosi, with subsequent RNA and protein analysis.
- Quantitative RT-PCR, immunoblotting, and gel shift assays were employed.
Main Results:
- Rosi mitigated LPS-induced suppression of Type II nuclear receptor-regulated genes, including bile acid transporters and Cyp3a11.
- Rosi prevented the inflammation-induced nuclear export of RXRalpha in both mice and HepG2 cells.
- This led to maintained nuclear RXRalpha levels and heterodimer binding activity.
Conclusions:
- Rosi directly counteracts the suppressive effects of inflammation on nuclear RXRalpha levels in the liver.
- Rosi exhibits a novel, direct anti-inflammatory action in hepatocytes.
Related Concept Videos
01:26Oral Hypoglycemic Agents: Biguanides and Glitazones
01:24Glucagon-like Receptor Agonists
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...
01:23Dipeptidyl Peptidase 4 Inhibitors
01:19Oral Hypoglycemic Agents: α-Glucosidase Inhibitors
Acarbose and miglitol are typically...