Role of TNF-α in ileum tight junction alteration in mouse model of restraint stress

Emanuela Mazzon, Salvatore Cuzzocrea

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Restraint stress induces permeability changes in the small intestine, but little is known about the role of tumor necrosis factor (TNF)-α in the defects of the TJ function. In the present study, we used tumor necrosis factor-R1 knockout mice (TNF-α-R1KO) to understand the roles of TNF-α on ileum altered permeability function in models of immobilization stress. The genetic TNF-α inhibition significantly reduced the degree of 1) TNF-α production in ileum tissues; 2) the alteration of zonula occludens-1 (ZO-1), claudin-2, claudin-4, claudin-5, and β-catenin (immunohistochemistry); and 3) apoptosis (TUNEL staining, Bax, Bcl-2 expression). Taken together, our results demonstrate that inhibition of TNF-α reduces the tight junction permeability in the ileum tissues associated with immobilization stress, suggesting a possible role of TNF-α on ileum barrier dysfunction.

Original languageEnglish
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume294
Issue number5
DOIs
Publication statusPublished - May 2008

Fingerprint

Tight Junctions
Ileum
Tumor Necrosis Factor-alpha
Permeability
Immobilization
Claudin-2
Claudin-4
Claudin-5
Catenins
In Situ Nick-End Labeling
Knockout Mice
Small Intestine
Immunohistochemistry
Apoptosis
Staining and Labeling

Keywords

  • β-catenin
  • Apoptosis
  • Claudin-2
  • Tight junction
  • TNF-α-deficient mice
  • Zonula occludens-1

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology
  • Hepatology
  • Physiology (medical)

Cite this

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abstract = "Restraint stress induces permeability changes in the small intestine, but little is known about the role of tumor necrosis factor (TNF)-α in the defects of the TJ function. In the present study, we used tumor necrosis factor-R1 knockout mice (TNF-α-R1KO) to understand the roles of TNF-α on ileum altered permeability function in models of immobilization stress. The genetic TNF-α inhibition significantly reduced the degree of 1) TNF-α production in ileum tissues; 2) the alteration of zonula occludens-1 (ZO-1), claudin-2, claudin-4, claudin-5, and β-catenin (immunohistochemistry); and 3) apoptosis (TUNEL staining, Bax, Bcl-2 expression). Taken together, our results demonstrate that inhibition of TNF-α reduces the tight junction permeability in the ileum tissues associated with immobilization stress, suggesting a possible role of TNF-α on ileum barrier dysfunction.",
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