KMID : 0043320160390101465
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Archives of Pharmacal Research 2016 Volume.39 No. 10 p.1465 ~ p.1471
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Isoliquiritigenin suppresses tumor necrosis factor-¥á-induced inflammation via peroxisome proliferator-activated receptor-¥ã in intestinal epithelial cells
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Jin Xing Yu
Sohn Dong-Hwan Lee Sung-Hee
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Abstract
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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¡Ç,4¡Ç-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-¥á (TNF-¥á) stimulated intestinal epithelium HT-29 cells. It also induced peroxisome proliferator-activated receptor-¥ã (PPAR¥ã) protein expression. Moreover, using a PPAR¥ã antagonist, GW9662, we found that the regulation of COX-2 and ICAM-1 expression by ISL in TNF-¥á-stimulated HT-29 cells is mediated via PPAR¥ã expression. A signal transduction study revealed that ISL significantly attenuates TNF-¥á-mediated JNK phosphorylation. ISL-induced ERK1/2 phosphorylation was associated with PPAR¥ã expression. Additionally, both the inhibitory effect on COX-2 and ICAM-1 expression and the induction of PPAR¥ã expression by ISL in TNF-¥á-stimulated HT-29 cells was abolished by the addition of U0126, a specific ERK1/2 inhibitor. Collectively, ISL-induced PPAR¥ã mediated, at least partially, the suppression of intestinal inflammation. These results suggest that ISL may be beneficial for the treatment of mucosal inflammation.
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KEYWORD
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Isoliquiritigenin, Inflammatory bowel diseases, Intestinal epithelial cells, Tumor necrosis factor-¥á, Peroxisome proliferator-activated receptor-¥ã
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