Blockade of TGF-β accelerates mucosal destruction through epithelial cell apoptosis

To clarify the protective role of transforming growth factor (TGF)-β for the intestinal epithelial injury in vivo, the effect of antibodies against TGF-β on epithelial destruction and apoptosis was assessed in dextran sulfate sodium (DSS)-induced colitis by histological analysis of colonic sections, account of apoptotic epithelial cells. To evaluate the pathways of epithelial apoptosis, we analyzed the activities of caspases, the level of Fas and cellular FLICE-inhibitory protein (cFLIP) expression in epithelial cells. Apoptotic epithelial cells were increased prior to the onset of ulceration in DSS-induced colitis, and the neutralization of TGF-β exacerbated epithelial apoptosis and histological damage score. The up-regulation of caspase-8 activity and Fas expression and reduced cFLIP expression were observed in intestinal epithelial cells from anti-TGF-β antibody-treated mice. The present study revealed that suppression of TGF-β deteriorated epithelial apoptosis, and the increase of apoptotic epithelial cells may amplify the inflammation in gut mucosa.