Green tea polyphenol (-)-epigallocatechin gallate blocks epithelial barrier dysfunction provoked by IFN-gamma but not by IL-4.
A characteristic of many enteropathies is increased epithelial permeability, a potentially pathophysiological event that can be evoked by T helper (Th)-1 (i.e., IFN-gamma) and Th2 (i.e., IL-4) cytokines and bacterial infection [e.g., enteropathogenic Escherichia coli (EPEC)]. The green tea polyphenol (-)-epigallocatechin gallate (EGCG) has immunosuppressive properties, and we hypothesized that it would ameliorate the increased epithelial permeability induced by IFN-gamma, IL-4, and/or EPEC. EGCG, but not the related epigallocatechin, completely prevented the increase in epithelial (i.e., T84 cell monolayer) permeability caused by IFN-gamma exposure as gauged by transepithelial resistance and horseradish peroxidase flux; EGCG did not alleviate the barrier disruption induced by IL-4 or EPEC. IFN-gamma-treated T84 and THP-1 (monocytic cell line) cells displayed STAT1 activation (tyrosine phosphorylation on Western blot analysis, DNA binding on EMSA) and upregulation of interferon response factor-1 mRNA, a STAT1-dependent gene. All three events were inhibited by EGCG pretreatment. Aurintricarboxylic acid also blocked IFN-gamma-induced STAT1 activation, but it did not prevent the increase in epithelial permeability. Additionally, pharmacological blockade of MAPK signaling did not affect IFN-gamma-induced epithelial barrier dysfunction. Thus, as a potential adjunct anti-inflammatory agent, EGCG can block STAT1-dependent events in gut epithelia and monocytes and prevent IFN-gamma-induced increased epithelial permeability. The latter event is both a STAT1- and MAPK-independent event.
Watson
James L
JL
Intestinal Disease Research Programme, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, L8N 3Z5, Canada.
Ansari
Sara
S
Cameron
Heather
H
Wang
Arthur
A
Akhtar
Mahmood
M
McKay
Derek M
DM
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D004926:Escherichia coli / Q000502:physiology; D005419:Flavonoids / Q000032:analysis / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism* / Q000382:microbiology; D010539:Permeability / Q000187:drug effects; D010636:Phenols / Q000032:analysis / Q000494:pharmacology; D059808:Polyphenols; D050794:STAT1 Transcription Factor; D050800:STAT6 Transcription Factor; D013662:Tea / Q000737:chemistry; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000378:metabolism
D000276:Adjuvants, Immunologic; D004268:DNA-Binding Proteins; D005419:Flavonoids; D007166:Immunosuppressive Agents; D010636:Phenols; D059808:Polyphenols; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D013662:Tea; D015534:Trans-Activators; D015847:Interleukin-4; D007371:Interferon-gamma; D002392:Catechin; C045651:epigallocatechin gallate