Loss of the tight junction protein ZO-1 in dextran sulfate sodium induced colitis.
BACKGROUND
Inflammatory bowel disease (IBD) is associated with increased intestinal permeability and decreased expression of tight junction (TJ) proteins in the inflamed mucosa. Whether this alteration in TJ expression is a prerequisite for the development of intestinal inflammation or a secondary result of that inflammation is unknown. This study looked at the expression of the TJ protein ZO-1 and the corresponding permeability changes in dextran sulfate sodium (DSS) induced colitis in a mouse model.


METHODS
BALB/c mice were fed 3% DSS or water for 1, 3, 5, or 7 days. The animals were weighed, stool was checked for blood, and the colon length measured. Segments of the colon were used for histology, immunohistochemistry for ZO-1, or Western blot for TJ proteins. Colonic permeability was measured using Evan's Blue dye.


RESULTS
DSS treated animals had heme positive stools, colitis by histology, significant weight loss, and colon shortening. There was an absence of ZO-1 by Western blot in the 7-day DSS treated animals, double the amount of claudin-1 and normal cytokeratin. The loss of ZO-1 started after 1 d of DSS treatment and was followed by a significant increase in permeability to Evan's blue by day 3.


CONCLUSIONS
The loss of ZO-1 and increased permeability preceded the development of significant intestinal inflammation suggesting that in DSS colitis alterations in the TJ complex occur before the intestinal inflammation and not as a consequence of it. These changes in the TJ complex may facilitate the development of the inflammatory infiltrate seen in colitis.
Poritz
Lisa S
LS
Department of Surgery and Department of Pathology, The Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, Pennsylvania 17033, USA. lporitz@psu.edu
Garver
Kristian I
KI
Green
Cecelia
C
Fitzpatrick
Leo
L
Ruggiero
Francesca
F
Koltun
Walter A
WA
D000818:Animals; D000925:Anticoagulants; D015153:Blotting, Western; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D003106:Colon / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D005243:Feces; D005260:Female; D005455:Fluorescent Antibody Technique; D006471:Gastrointestinal Hemorrhage / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010750:Phosphoproteins / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism* / Q000473:pathology*; D015431:Weight Loss; D062826:Zonula Occludens-1 Protein
D000925:Anticoagulants; D008565:Membrane Proteins; D010750:Phosphoproteins; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D016264:Dextran Sulfate