Isoliquiritigenin suppresses tumor necrosis factor-α-induced inflammation via peroxisome proliferator-activated receptor-γ in intestinal epithelial cells.
Mots clés
Abstrait
Intestinal epithelial cells play an important role in the mucosal immune reaction in inflammatory bowel diseases via the expression of inflammatory mediators, such as cyclooxygenase-2 (COX-2) and intercellular adhesion molecule-1 (ICAM-1). Isoliquiritigenin (ISL; 4,2',4'-trihydroxychalcone) has been shown to exhibit anti-inflammatory properties in murine macrophage cells. In the present study, we evaluated the anti-inflammatory properties of ISL in intestinal epithelial cells and determined its mechanism of action. ISL suppressed the expression of COX-2 and ICAM-1 in tumor necrosis factor-α (TNF-α) stimulated intestinal epithelium HT-29 cells. It also induced peroxisome proliferator-activated receptor-γ (PPARγ) protein expression. Moreover, using a PPARγ antagonist, GW9662, we found that the regulation of COX-2 and ICAM-1 expression by ISL in TNF-α-stimulated HT-29 cells is mediated via PPARγ expression. A signal transduction study revealed that ISL significantly attenuates TNF-α-mediated JNK phosphorylation. ISL-induced ERK1/2 phosphorylation was associated with PPARγ expression. Additionally, both the inhibitory effect on COX-2 and ICAM-1 expression and the induction of PPARγ expression by ISL in TNF-α-stimulated HT-29 cells was abolished by the addition of U0126, a specific ERK1/2 inhibitor. Collectively, ISL-induced PPARγ mediated, at least partially, the suppression of intestinal inflammation. These results suggest that ISL may be beneficial for the treatment of mucosal inflammation.