Role of TNF-alpha in gut mucosal changes after severe burn.
Gut epithelial cell death by apoptosis is increased in the gut epithelium after severe burn associated with mucosal atrophy. We hypothesized that tumor necrosis factor (TNF)-alpha-TNF receptor (TNFR) interaction activates apoptosis in small bowel mucosal cells after severe burn. C57BL6 mice received a 30% total body surface area scald burn and were treated with neutralizing anti-TNF-alpha. The proximal small bowel was assessed for mucosal atrophy. Proliferation and apoptosis of mucosal cells were assessed by proliferative cell nuclear antigen-immunostaining and terminal deoxyuridine nick-end labeling assay, respectively. Mucosal height and mucosal cell number decreased after burn. Anti-TNF-alpha-treated mice showed significantly less mucosal atrophy. Proliferation of intestinal cells was not changed with burn or anti-TNF-alpha treatment. An over threefold increase in apoptotic cell number was seen after burn, which was diminished by anti-TNF-alpha treatment. Changes in gut mucosal homeostasis after severe burn are affected, in part, by the activation of apoptosis by TNF-alpha-TNFR interaction.
Shriners Hospitals for Children and Department of Surgery, University of Texas Medical Branch, Galveston, Texas 77550, USA.
Marcus
M
Spies
Vicky L
VL
Chappell
Mohan R
MR
Dasu
David N
DN
Herndon
James C
JC
Thompson
Steven E
SE
Wolf
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001284:Atrophy; D002056:Burns / Q000473:pathology / Q000503:physiopathology*; D020287:In Situ Nick-End Labeling; D007413:Intestinal Mucosa / Q000473:pathology / Q000503:physiopathology*; D007421:Intestine, Small / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D015599:Trauma Severity Indices; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology*
D000906:Antibodies; D018809:Proliferating Cell Nuclear Antigen; D014409:Tumor Necrosis Factor-alpha