Dislocation of tight junction proteins without F-actin disruption in inactive Crohn's disease.
Crohn's disease is associated with increased permeability of the intestinal barrier even in quiescent patients. Increased intestinal permeability may cause dysregulated immunological responses in the intestinal mucosa that leads to chronic intestinal inflammation. We have studied the expression of tight junction proteins (occludin and zonula occludens), alpha2-smooth muscle actin, TGF-beta with a cytoskeletal protein (F-actin) in the intestinal epithelium of patients with inflammatory bowel disease. Surgical samples were obtained from 6 controls (individuals without inflammatory bowel disease), 8 patients with ulcerative colitis and 7 patients with Crohn's disease. F-actin was visualized with fluorescein phalloidin. Tight junction proteins, alpha2 smooth muscle actin, and TGFbeta were visualized by the immunofluorescent method. Occludin and zonula occludens found in apical tight junctions in normal epithelium were dislocated to the basolateral position and in the lamina propria extracellular matrix in patients with Crohn's disease, while the structure of F-actin was maintained in inactive or minimally inflamed mucosa. TGF-beta positive inflammatory cells were increased in ulcerative colitis and Crohn's disease mucosa. Subepithelial myofibroblasts were constitutively found in controls, ulcerative colitis, and Crohn's disease mucosa. Latent dislocation of tight junction proteins, without disturbance of the cytoskeleton in the inactive mucosa of patients with Crohn's disease, may permit the invasion of gut antigens because the functional disruption of tight junctions could initiate an altered immune response.
Oshitani
Nobuhide
N
Third Department of Internal Medicine, Osaka City University Medical School, Abeno-ku, Osaka 545-8585, Japan. nobu@med.osaka-cu.ac.jp
Watanabe
Kenji
K
Nakamura
Shiro
S
Fujiwara
Yasuhiro
Y
Higuchi
Kazuhide
K
Arakawa
Tetsuo
T
D000199:Actins / Q000378:metabolism*; D003424:Crohn Disease / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D062793:Occludin; D010750:Phosphoproteins / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D062826:Zonula Occludens-1 Protein
D000199:Actins; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D010750:Phosphoproteins; C569042:TJP1 protein, human; D016212:Transforming Growth Factor beta; D062826:Zonula Occludens-1 Protein