Attenuation of Colonic Inflammation by PPARγ in Intestinal Epithelial Cells: Effect on Toll-like Receptor Pathway
- 1 April 2006
- journal article
- research article
- Published by Springer Science and Business Media LLC in Digestive Diseases and Sciences
- Vol. 51 (4), 693-697
- https://doi.org/10.1007/s10620-006-3193-0
Abstract
The peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor highly expressed in the colon and playing an anti-inflammatory role through inhibition of the NF-κB pathway. Toll-like receptor 4 (TLR4) has been known to mediate LPS-induced cellular signaling through activation of NF-κB pathway in intestinal epithelial cells. The aims of this study were to evaluate attenuation of inflammation by PPARγ in intestinal epithelial cells and to study the possible relation between PPARγ and TLR4. HT-29 human epithelial cells were stimulated with LPS (20 μg/ml) and PPARγ ligand, 15d-PGJ2 (10 μM), or with LPS (20 μg/ml) alone for 24 hr. COX-2, IL-8, TLR4, and PPARγ mRNA expression was assessed by RT-PCR. IL-8 protein levels and TLR4 protein expression were analyzed by ELISA and Western blot, respectively. To evaluate the action mechanisms of PPARγ ligand, Western blot analysis for IκBα degradation was performed. Costimulation with LPS and PPARγ ligand in comparison to LPS stimulation alone (1) decreased COX-2, IL-8 mRNA expression and IL-8 protein secretion, (2) decreased TLR4 mRNA and protein expression, and (3) decreased PPARγ mRNA expression. PPARγ ligand delayed LPS-induced IκBα degradation. These findings suggest that PPAR-γ ligands suppress inflammation in intestinal epithelial cells. PPARγ and TLR, these two antagonistic signaling pathways in intestinal epithelial cells may be partially cross-linked.Keywords
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