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Isoliquiritigenin suppresses tumor necrosis factor-α-induced inflammation via peroxisome proliferator-activated receptor-γ in intestinal epithelial cells

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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.

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Acknowledgments

This study was supported by a Grant from Wonkwang University for Prof. Sung Hee Lee (2015).

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Authors and Affiliations

  1. College of Pharmacy, Institute of Pharmaceutical Research and Development, Wonkwang University, Iksan, Jeonbuk, 54538, South Korea

    Xing Yu Jin, Dong Hwan Sohn & Sung Hee Lee

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  1. Xing Yu Jin
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  2. Dong Hwan Sohn
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  3. Sung Hee Lee
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Correspondence to Sung Hee Lee.

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Jin, X.Y., Sohn, D.H. & Lee, S.H. Isoliquiritigenin suppresses tumor necrosis factor-α-induced inflammation via peroxisome proliferator-activated receptor-γ in intestinal epithelial cells. Arch. Pharm. Res. 39, 1465–1471 (2016). https://doi.org/10.1007/s12272-016-0805-x

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