title: Tumor necrosis factor induces developmental stage-dependent structural changes in the immature small intestine.
abstract: BACKGROUND
  Premature infants are commonly subject to intestinal inflammation. Since the human small intestine does not reach maturity until term gestation, premature infants have a unique challenge, as either acute or chronic inflammation may alter the normal development of the intestinal tract. Tumor necrosis factor (TNF) has been shown to acutely alter goblet cell numbers and villus length in adult mice. In this study we tested the effects of TNF on villus architecture and epithelial cells at different stages of development of the immature small intestine.
  
  
  METHODS
  To examine the effects of TNF-induced inflammation, we injected acute, brief, or chronic exposures of TNF in neonatal and juvenile mice.
  
  
  RESULTS
  TNF induced significant villus blunting through a TNF receptor-1 (TNFR1) mediated mechanism, leading to loss of villus area. This response to TNFR1 signaling was altered during intestinal development, despite constant TNFR1 protein expression. Acute TNF-mediated signaling also significantly decreased Paneth cells.
  
  
  CONCLUSIONS
  Taken together, the morphologic changes caused by TNF provide insight as to the effects of inflammation on the developing intestinal tract. Additionally, they suggest a mechanism which, coupled with an immature immune system, may help to explain the unique susceptibility of the immature intestine to inflammatory diseases such as NEC.
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Kathryn S
authors.initials: KS
authors.lastname: Brown
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Huiyu
authors.identifier: 0000-0001-7797-969X
authors.initials: H
authors.lastname: Gong
authors.affiliation: Departments of Pediatrics and Biochemistry and Molecular Biology, University of Southern California Keck School of Medicine and The Saban Research Institute at Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Frey
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Brock
authors.identifier: 0000-0002-1750-688X
authors.initials: B
authors.lastname: Pope
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Matthew
authors.identifier: 0000-0003-0952-4110
authors.initials: M
authors.lastname: Golden
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Katerina
authors.initials: K
authors.lastname: Martin
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Mitchel
authors.initials: M
authors.lastname: Obey
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: McElroy
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D006801:Humans; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics / Q000378:metabolism*; D048069:Tumor Necrosis Factors / Q000494:pharmacology*
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D048069:Tumor Necrosis Factors