@article{TEXTUAL,
      recid = {10513},
      author = {Kolodziej, Lauren E. and Lodolce, James P. and Chang,  Jonathan E. and Schneider, Jeffrey R. and Grimm, Wesley A.  and Bartulis, Sarah J. and Zhu, Xiaorong and Messer,  Jeannette S. and Murphy, Stephen F. and Reddy, Nishith and  Turner, Jerrold R. and Boone, David L.},
      title = {TNFAIP3 Maintains Intestinal Barrier Function and Supports  Epithelial Cell Tight Junctions},
      journal = {PLOS ONE},
      address = {2011-10-21},
      number = {TEXTUAL},
      abstract = {<p>Tight junctions between intestinal epithelial cells  mediate the permeability of the intestinal barrier, and  loss of intestinal barrier function mediated by TNF  signaling is associated with the inflammatory  pathophysiology observed in Crohn's disease and celiac  disease. Thus, factors that modulate intestinal epithelial  cell response to TNF may be critical for the maintenance of  barrier function. TNF alpha-induced protein 3 (TNFAIP3) is  a cytosolic protein that acts in a negative feedback loop  to regulate cell signaling induced by Toll-like receptor  ligands and TNF, suggesting that TNFAIP3 may play a role in  regulating the intestinal barrier. To investigate the  specific role of TNFAIP3 in intestinal barrier function we  assessed barrier permeability in TNFAIP3<sup>−/−</sup> mice  and LPS-treated villin-TNFAIP3 transgenic mice.  TNFAIP3<sup>−/−</sup> mice had greater intestinal  permeability compared to wild-type littermates, while  villin-TNFAIP3 transgenic mice were protected from  increases in permeability seen within LPS-treated wild-type  littermates, indicating that barrier permeability is  controlled by TNFAIP3. In cultured human intestinal  epithelial cell lines, TNFAIP3 expression regulated both  TNF-induced and myosin light chain kinase-regulated tight  junction dynamics but did not affect myosin light chain  kinase activity. Immunohistochemistry of mouse intestine  revealed that TNFAIP3 expression inhibits LPS-induced loss  of the tight junction protein occludin from the apical  border of the intestinal epithelium. We also found that  TNFAIP3 deubiquitinates polyubiquitinated occludin. These  <em>in vivo</em> and <em>in vitro</em> studies support the  role of TNFAIP3 in promoting intestinal epithelial barrier  integrity and demonstrate its novel ability to maintain  intestinal homeostasis through tight junction protein  regulation.</p>},
      url = {http://knowledge.uchicago.edu/record/10513},
}