Tumor necrosis factor induces developmental stage-dependent structural changes in the immature small intestine

Kathryn S Brown; Huiyu Gong; Mark R Frey; Brock Pope; Matthew Golden; Katerina Martin; Mitchel Obey; Steven J McElroy

doi:10.1155/2014/852378

Back

Tumor necrosis factor induces developmental stage-dependent structural changes in the immature small intestine

Journal article

Open access

Peer reviewed

Tumor necrosis factor induces developmental stage-dependent structural changes in the immature small intestine

Kathryn S Brown, Huiyu Gong, Mark R Frey, Brock Pope, Matthew Golden, Katerina Martin, Mitchel Obey and Steven J McElroy

Mediators of inflammation, Vol.2014(8), pp.852378-11

2014

DOI: 10.1155/2014/852378

PMCID: PMC4163315

PMID: 25242872

Files and links (1)

url

https://doi.org/10.1155/2014/852378View

Published (Version of record) Open Access

Abstract

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. To examine the effects of TNF-induced inflammation, we injected acute, brief, or chronic exposures of TNF in neonatal and juvenile mice. 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. 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.

Apoptosis - drug effects

Humans

Receptors, Tumor Necrosis Factor, Type I - metabolism

Receptors, Tumor Necrosis Factor, Type I - genetics

Receptors, Tumor Necrosis Factor, Type II - genetics

Blotting, Western

Mice, Knockout

Animals

Receptors, Tumor Necrosis Factor, Type II - metabolism

Intestine, Small - drug effects

Polymerase Chain Reaction

Mice

Intestine, Small - metabolism

Tumor Necrosis Factors - pharmacology

Details

Title: Subtitle: Tumor necrosis factor induces developmental stage-dependent structural changes in the immature small intestine
Creators: Kathryn S Brown - Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA
Huiyu Gong - Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA
Mark R Frey - 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
Brock Pope - Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA
Matthew Golden - Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA
Katerina Martin - Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA
Mitchel Obey - Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA
Steven J McElroy - Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Mediators of inflammation, Vol.2014(8), pp.852378-11
DOI: 10.1155/2014/852378
PMID: 25242872
PMCID: PMC4163315
NLM abbreviation: Mediators Inflamm
ISSN: 0962-9351
eISSN: 1466-1861
Grant note: R03 DK097335 / NIDDK NIH HHS DK095004 / NIDDK NIH HHS DK097335 / NIDDK NIH HHS DK083677 / NIDDK NIH HHS K08 DK083677 / NIDDK NIH HHS R01 DK095004 / NIDDK NIH HHS L40 DK084865 / NIDDK NIH HHS
Language: English
Date published: 2014
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Internal Medicine
Record Identifier: 9984093498502771

Metrics

12 Record Views

12 Times Cited - Web of Science