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TNFAIP3 maintains intestinal barrier function and supports epithelial cell tight junctions
Lauren E Kolodziej1, James P Lodolce, Jonathan E Chang
1Department of Medicine, University of Chicago, Chicago, Illinois, United States of America.
Plos One
|October 28, 2011
Summary
Tumor necrosis factor alpha-induced protein 3 (TNFAIP3) is crucial for maintaining intestinal barrier integrity. This protein regulates tight junctions, preventing increased permeability associated with inflammatory diseases like Crohn's disease.
Area of Science:
- Gastroenterology
- Immunology
- Cell Biology
Background:
- Intestinal epithelial tight junctions are vital for barrier function.
- Loss of barrier function, mediated by TNF signaling, is implicated in Crohn's and celiac diseases.
- Tumor necrosis factor alpha-induced protein 3 (TNFAIP3) regulates TNF signaling.
Purpose of the Study:
- To investigate the role of TNFAIP3 in regulating intestinal barrier function.
- To determine how TNFAIP3 influences intestinal epithelial cell responses to TNF.
Main Methods:
- Assessed intestinal permeability in TNFAIP3 knockout mice and transgenic mice.
- Utilized cultured human intestinal epithelial cell lines.
- Performed immunohistochemistry on mouse intestine tissue.
- Investigated TNFAIP3's effect on occludin and its ubiquitination status.
Main Results:
- TNFAIP3 knockout mice exhibited increased intestinal permeability.
- Transgenic mice overexpressing TNFAIP3 were protected from LPS-induced permeability increases.
- TNFAIP3 regulated TNF-induced tight junction dynamics in cell lines.
- TNFAIP3 inhibits LPS-induced loss of occludin and deubiquitinates occludin.
Conclusions:
- TNFAIP3 plays a critical role in maintaining intestinal epithelial barrier integrity.
- TNFAIP3 promotes intestinal homeostasis by regulating tight junction proteins, particularly occludin.
- TNFAIP3 represents a potential therapeutic target for inflammatory bowel diseases.
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