Epithelial barrier defects in HT-29/B6 colonic cell monolayers induced by tumor necrosis factor-alpha.
The barrier function of intestinal epithelia relies upon the continuity of the enterocyte monolayer and intact tight junctions. After incubation with tumor necrosis factor-alpha TNF-alpha, however, the number of strands that form the tight junctions decreases, and apoptosis is induced in intestinal epithelial cells. These morphological changes lead to a rise of transepithelial ion permeability, because the paracellular ion permeability increases and leaks associated with sites of apoptosis increase by number and magnitude. Thus apoptosis and degradation of tight junctions contribute to the increased permeability observed after exposure to TNF-alpha. These mechanisms explain clinical manifestations in the inflamed intestinal wall containing cytokine-secreting macrophages--for example, leak flux diarrhea and invasion of bacterial enterotoxins.
Gitter
A H
AH
Institut für Klinische Physiologie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, 12200 Berlin, Germany. gitter@medizin.fu-berlin.de
Bendfeldt
K
K
Schmitz
H
H
Schulzke
J D
JD
Bentzel
C J
CJ
Fromm
M
M
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D003106:Colon / Q000166:cytology*; D004594:Electrophysiology; D004847:Epithelial Cells / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D008854:Microscopy, Electron; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha