Blockade of TGF-β accelerates mucosal destruction through epithelial cell apoptosis
| Autor: | Hirotake Sakuraba, Kazufumi Yamagata, Yoh Ishiguro, Akio Nakane, Akihiro Munakata |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Biophysics
Apoptosis Inflammation Biochemistry Mice Transforming Growth Factor beta In vivo medicine Animals fas Receptor Intestinal Mucosa Colitis Molecular Biology Caspase Caspase 8 Mice Inbred BALB C Mucous Membrane biology Dextran Sulfate Antibodies Monoclonal Epithelial Cells Cell Biology medicine.disease Intestines Immunology Cancer research biology.protein Female Signal transduction Antibody medicine.symptom Signal Transduction Transforming growth factor |
| Zdroj: | Biochemical and Biophysical Research Communications. 359:406-412 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2007.05.117 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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