Blockade of TGF-beta accelerates mucosal destruction through epithelial cell apoptosis.
To clarify the protective role of transforming growth factor (TGF)-beta for the intestinal epithelial injury in vivo, the effect of antibodies against TGF-beta 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-beta 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-beta antibody-treated mice. The present study revealed that suppression of TGF-beta deteriorated epithelial apoptosis, and the increase of apoptotic epithelial cells may amplify the inflammation in gut mucosa.
Sakuraba
Hirotake
H
Department of Microbiology and Immunology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan.
Ishiguro
Yoh
Y
Yamagata
Kazufumi
K
Munakata
Akihiro
A
Nakane
Akio
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis; D053181:Caspase 8 / Q000378:metabolism; D016264:Dextran Sulfate / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000166:cytology / Q000187:drug effects / Q000293:injuries / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism
D000911:Antibodies, Monoclonal; D016212:Transforming Growth Factor beta; D019014:fas Receptor; D016264:Dextran Sulfate; D053181:Caspase 8