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Flavonoids exert distinct modulatory actions on cyclooxygenase 2 and NF‐κB in an intestinal epithelial cell line (IEC18)
Author(s) -
LópezPosadas R,
Ballester I,
Mascaraque C,
Suárez MD,
Zarzuelo A,
MartínezAugustin O,
Sánchez de Medina F
Publication year - 2010
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2010.00827.x
Subject(s) - signal transduction , western blot , kinase , cyclooxygenase , p38 mitogen activated protein kinases , phosphorylation , biology , mapk/erk pathway , lipopolysaccharide , cell culture , nf κb , microbiology and biotechnology , iκbα , inflammation , biochemistry , immunology , enzyme , gene , genetics
Background and purpose: Cyclooxygenase 2 (COX‐2) is involved in inflammatory bowel disease, but the effect of flavonoids at the intestinal epithelial level is unknown. We aimed to characterize the effect and structure‐activity relationship of nine selected flavonoids on COX‐2 expression in intestinal epithelial cell (IEC)18 cells. We also investigated the signal transduction pathway(s) responsible for the effects observed. Experimental approach: Intestinal epithelial cell 18, a non‐tumour cell line with intestinal epithelial phenotype, was used. COX‐2 was measured by Western blot and the involvement of the NF‐κB pathway assessed by Western blot, pharmacological inhibition, luciferase reporter assays and nuclear translocation experiments. Key results: The effect of flavonoids on COX‐2 expression depended on the experimental conditions tested [non‐stimulated and lipopolysaccharide (LPS)‐stimulated]. Flavonoids caused an increase in COX‐2 expression and NF‐κB‐dependent gene transcription under basal conditions. Conversely, under LPS stimulation flavonoids increased, decreased or did not affect COX‐2 levels depending on the specific type. Variable effects were observed on extracellular signal regulated kinase/p38/c‐Jun N‐terminal kinase phosphorylation and p50/65 nuclear translocation. Conclusion and implications: The effect of flavonoids on COX‐2 expression depended on the balance of the interference with IκB‐α phosphorylation and other signalling targets, and therefore depends on the experimental conditions and on the type of flavonoids. This is expected to result in different effects in inflammatory conditions. In general, flavonoids may limit epithelial COX‐2 expression in inflammatory conditions while favouring it when inflammation is not present.