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Updated: Jun 4, 2026

Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin
Published on: September 12, 2019
Bowel necrosis induced by tumor necrosis factor in rats is mediated by platelet-activating factor
1Department of Pathology, Children's Memorial Hospital, Northwestern University, Chicago, Illinois 60614.
Abstract:
We have developed a rat model of ischemic bowel necrosis associated with shock by injection of platelet-activating factor (PAF) or a combination of PAF and endotoxin. Recent investigations have shown that tumor necrosis factor (TNF) also induces shock and necrosis of the gastrointestinal tract. The morphological changes of TNF-induced bowel lesions are indistinguishable from those caused by PAF. The mechanism of TNF-induced bowel necrosis is unclear. In the present study, we have shown that (a) TNF caused PAF production in bowel tissue; (b) the effects of TNF and LPS on PAF production in the intestine are additive; (c) TNF and LPS are synergistic in inducing bowel necrosis; and (d) TNF-induced bowel necrosis is due to PAF release and can be prevented by pretreatment with PAF antagonists.
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