In intestinal epithelia, tight junctions (TJs) normally block paracellular transport (movement between cells) of antigens and solutes from the intestinal lumen to the mucosal layer. In inflammatory bowel disease (IBD), TJ perturbation means that antigens come into contact with immune system cells in the mucosal layer, which causes inflammation and diarrhoea. Now, on page 4145, Jörg-Dieter Schulzke and colleagues provide new insights into intestinal TJ regulation, and suggest a new therapeutic approach for IBD. The authors investigate the effect of TNFα (a cytokine that has pro-inflammatory effects on transepithelial resistance and TJs) and berberine (a herbal antidiarrhoeal agent) on human intestinal cell monolayers and rat colon preparations. TNFα reduces the paracellular resistance of intestinal cell layers and increases their paracellular permeability, the authors report, but does not affect their transcellular resistance. Furthermore, TNFα removes claudin-1 (a TJ tightening protein) from the TJs and increases the expression of claudin-2 (a pore-forming protein). Notably, berberine completely antagonises TNFα-induced barrier changes in both models, its effects being mediated through tyrosine kinase, Akt and NFκB signalling. Together, these results provide an explanation for berberine's antidiarrhoeal action that could aid the design of new IBD therapeutics.
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