Catechols in caffeic acid phenethyl ester are essential for inhibition of TNF-mediated IP-10 expression through NF-κB-dependent but HO-1- and p38-independent mechanisms in mouse intestinal epithelial cells

Authors

  • Job O. Mapesa,

    1. Chair for Biofunctionality, ZIEL – Research Center for Nutrition and Food Sciences, CDD – Center for Diet and Disease, Technische Universität München, Freising-Weihenstephan, Germany
    2. Dairy and Food Science Department, Egerton University, Njoro, Kenya
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  • Nadine Waldschmitt,

    1. Chair for Biofunctionality, ZIEL – Research Center for Nutrition and Food Sciences, CDD – Center for Diet and Disease, Technische Universität München, Freising-Weihenstephan, Germany
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  • Ingrid Schmoeller,

    1. Chair for Biofunctionality, ZIEL – Research Center for Nutrition and Food Sciences, CDD – Center for Diet and Disease, Technische Universität München, Freising-Weihenstephan, Germany
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  • Carolin Blume,

    1. Chair for Biofunctionality, ZIEL – Research Center for Nutrition and Food Sciences, CDD – Center for Diet and Disease, Technische Universität München, Freising-Weihenstephan, Germany
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  • Thomas Hofmann,

    1. Food Chemistry and Molecular Sensory Science, ZIEL – Research Center for Nutrition and Food Sciences, Technische Universität München, Freising-Weihenstephan, Germany
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  • Symon Mahungu,

    1. Dairy and Food Science Department, Egerton University, Njoro, Kenya
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  • Thomas Clavel,

    1. Chair for Biofunctionality, ZIEL – Research Center for Nutrition and Food Sciences, CDD – Center for Diet and Disease, Technische Universität München, Freising-Weihenstephan, Germany
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  • Dirk Haller

    Corresponding author
    1. Chair for Biofunctionality, ZIEL – Research Center for Nutrition and Food Sciences, CDD – Center for Diet and Disease, Technische Universität München, Freising-Weihenstephan, Germany
    • Chair for Biofunctionality, ZIEL – Research Center for Nutrition and Food Sciences, Technische Universität München, Gregor-Mendel Str. 2, 85350 Freising-Weihenstephan, Germany Fax: +49-8161-71-2824
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Abstract

Scope: Caffeic acid phenethyl ester (CAPE) is an active constituent of honeybee propolis inhibiting nuclear factor (NF)-κB. The aims of our study were to provide new data on the functional relevance and mechanisms underlying the role of CAPE in regulating inflammatory processes at the epithelial interface in the gut and to determine the structure/activity relationship of CAPE.

Methods and results: CAPE significantly inhibited TNF-induced IP-10 expression in intestinal epithelial cells. Using various analogues, we demonstrated that substitution of catechol hydroxyl groups and addition of one extra hydroxyl group on ring B reversed the functional activity of CAPE to inhibit IP-10 production. The anti-inflammatory potential of CAPE was confirmed in ileal tissue explants and embryonic fibroblasts derived from TNFΔARE/+ mice. Interestingly, CAPE inhibited both TNF- and LPS-induced IP-10 production in a dose-dependent manner, independently of p38 MAPK, HO-1 and Nrf2 signaling pathways. We found that CAPE did not inhibit TNF-induced IκB phosphorylation/degradation or nuclear translocation of RelA/p65, but targeted downstream signaling events at the level of transcription factor recruitment to the gene promoter.

Conclusion: This study reveals the structure–activity effects and anti-inflammatory potential of CAPE in the intestinal epithelium.

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