Epithelial apoptosis is a prominent feature of the epithelial barrier disturbance in intestinal inflammation: effect of pro-inflammatory interleukin-13 on epithelial cell function.
In ulcerative colitis, the T helper type 2 proinflammatory cytokine Interleukin-13 (IL-13) contributes as effector cytokine to the epithelial changes associated with disturbed epithelial barrier function. This study aimed to investigate the underlying mechanisms in a colonic epithelial cell culture model. For studying these epithelial features in response to proinflammatory cytokines epithelial apoptosis was investigated by TdT-mediated X-dUTP nick end labeling (TUNEL) staining in HT-29/B6 cell monolayers. In contrast to interferon-gamma, IL-13 significantly upregulated the apoptotic rate of cells, which was intensified by simultaneous exposure to tumor necrosis factor-alpha. That this has a direct functional influence on epithelial barrier was shown by the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp, which inhibited IL-13 induced apoptosis induction and concomitantly reversed the decrease in epithelial resistance by approximately 50%. Direct evidence for apoptotic rosettes at corresponding sites of barrier defects in the epithelium was obtained by conductance scanning. In addition, the pore-forming tight junction protein claudin-2 was found to be upregulated at protein and mRNA level. In conclusion, IL-13 disturbs intestinal barrier function through mechanisms including apoptosis induction and alteration of tight junction protein composition.
Heller
F
F
Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité, Campus Benjamin Franklin, Berlin, Germany.
Fromm
A
A
Gitter
A H
AH
Mankertz
J
J
Schulzke
J-D
JD
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D002460:Cell Line; D057167:Claudins; D016207:Cytokines / Q000276:immunology; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D004848:Epithelium / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000473:pathology; D018836:Inflammation Mediators / Q000276:immunology; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D018793:Interleukin-13 / Q000276:immunology* / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D019108:Tight Junctions / Q000276:immunology / Q000378:metabolism
C491875:CLDN2 protein, human; D057167:Claudins; D016207:Cytokines; D018836:Inflammation Mediators; D018793:Interleukin-13; D008565:Membrane Proteins