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Involvement of tumor necrosis factor alpha in intestinal epithelial cell proliferation following Paneth cell destruction.

Abstract：

BACKGROUND:An intravenous injection of diphenylthiocarbazone (dithizone), a zinc chelator, induces selective killing of Paneth cells which have a large amount of zinc in their cytoplasmic granules. A transient wave of intestinal epithelial cell proliferation occurs at 12 h after the injection. Paneth cells have tumor necrosis factor (TNF)-alpha protein in their cytoplasmic granules, and TNF-alpha has a proliferative effect on intestinal epithelial cells in vitro. The aim of this study is to clarify the in vivo role of TNF-alpha in intestinal epithelial cell proliferation using a dithizone-treated rat model. METHODS:Male Wistar rats received a dithizone (100 mg/kg of body weight) injection with or without TNF-alpha inhibitor, pentoxifylline (100 mg/kg), neutralizing anti-TNF-alpha antibody (2 mg/kg), or nuclear transcription factor kappaB (NF-kappaB) inhibitors: pyrrolidine dithiocarbamate (100 mg/kg) or N-acetyl-L-cystein (100 mg/kg). The activation of NF-kappaB was examined by the electrophoretic mobility shift assay, and cellular proliferation by BrdU labeling. RESULTS:Without any inhibitors, dithizone treatment evoked NF-kappaB activation in the ileal mucosa with its peak level at 2 h after the injection. TNF-alpha inhibition reduced the NF-kappaB activation, and blocked a transient wave of epithelial cell proliferation 12 h after the injection. NF-kappaB inhibitors also reduced the NF-kappaB activation and epithelial cell proliferation. CONCLUSIONS:TNF-alpha released from degenerated Paneth cells was, in part, responsible for the intestinal cell proliferation through the activation of NF-kappaB, suggesting its proliferative effect on intestinal epithelial cells.

journal_name

Scand J Gastroenterol

journal_title

Scandinavian journal of gastroenterology

authors

Seno H,Sawada M,Fukuzawa H,Morita-Fujisawa Y,Takaishi S,Hiai H,Chiba T

doi

10.1080/003655202753416803

subject

Has Abstract

pub_date

2002-02-01 00:00:00

pages

154-60

issue

2

eissn

0036-5521

issn

1502-7708

journal_volume

37

pub_type

杂志文章

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