Running Title: EGCG blocks IFNγ induced epithelial hyper-permeability *Address correspondence to:

A characteristic of many enteropathies is increased epithelial permeability, a potentially pathophysiological event that can be evoked by T helper (Th)-1 (i.e. IFNγ) and Th2 (i.e. IL-4) cytokines, and bacterial infection (e.g. enteropathogenic E. coli (EPEC)). The green tea polyphenol, (-)-epigallocatechin gallate (EGCG), has immunosuppressive properties and we hypothesised that it would ameliorate the increased epithelial permeability induced by IFNγ, IL-4 and/or EPEC. EGCG, but not the related EGC, completely prevented the increase in epithelial (i.e. T84 cell monolayer) permeability caused by IFNγ exposure, as gauged by transepithelial resistance and horse-radish peroxidase flux; EGCG did not alleviate the barrier disruption induced by IL-4 or EPEC. IFNγ−treated T84 and THP-1 (monocytic cell line) cells displayed STAT1 activation (tyrosine phosphorylation on western blot, DNA binding on EMSA) and up-regulation of interferon response factor (IRF)-1 mRNA, a STAT1-dependent gene: all three events were inhibited by EGCG pre-treatment. Aurintricarboxylic acid also blocked IFNγ-induced STAT1 activation but it did not prevent the increase in epithelial permeability. Additionally, pharmacological blockade of MAPK signalling did not affect IFNγ-induced epithelial barrier dysfunction. Thus, as a potential adjunct anti-inflammatory agent, EGCG ca