title: Isoliquiritigenin suppresses tumor necrosis factor-α-induced inflammation via peroxisome proliferator-activated receptor-γ in intestinal epithelial cells.
abstract: 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.
authors.affiliation: College of Pharmacy, Institute of Pharmaceutical Research and Development, Wonkwang University, Iksan, Jeonbuk, 54538, South Korea.
authors.forename: Xing Yu
authors.initials: XY
authors.lastname: Jin
authors.affiliation: College of Pharmacy, Institute of Pharmaceutical Research and Development, Wonkwang University, Iksan, Jeonbuk, 54538, South Korea.
authors.forename: Dong Hwan
authors.initials: DH
authors.lastname: Sohn
authors.affiliation: College of Pharmacy, Institute of Pharmaceutical Research and Development, Wonkwang University, Iksan, Jeonbuk, 54538, South Korea. gsseo@wku.ac.kr.
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Lee
mesh_terms: D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D047188:Chalcones / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D047495:PPAR gamma / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000633:toxicity*
chemical_list: D047188:Chalcones; D018836:Inflammation Mediators; D047495:PPAR gamma; D014409:Tumor Necrosis Factor-alpha; C040920:isoliquiritigenin
keywords: Inflammatory bowel diseases; Intestinal epithelial cells; Isoliquiritigenin; Peroxisome proliferator-activated receptor-γ; Tumor necrosis factor-α