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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.
MedLine Citation:
PMID:  22038897     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 TNF(ΔARE/+) 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.
Authors:
Job O Mapesa; Nadine Waldschmitt; Ingrid Schmoeller; Carolin Blume; Thomas Hofmann; Symon Mahungu; Thomas Clavel; Dirk Haller
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-31
Journal Detail:
Title:  Molecular nutrition & food research     Volume:  -     ISSN:  1613-4133     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101231818     Medline TA:  Mol Nutr Food Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Affiliation:
Chair for Biofunctionality, ZIEL - Research Center for Nutrition and Food Sciences, CDD - Center for Diet and Disease, Technische Universität München, Freising-Weihenstephan, Germany; Dairy and Food Science Department, Egerton University, Njoro, Kenya.
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