The significance of interferon-gamma-triggered internalization of tight-junction proteins in inflammatory bowel disease.
Disruption of the epithelial barrier function of tight junctions by the proinflammatory cytokine interferon (IFN)-gamma plays a fundamental role in the pathogenesis of inflammatory bowel disease and other gastrointestinal disorders, but its precise mechanism has not been established. This Perspective provides an overview of how IFN-gamma triggers barrier dysfunction and bacterial translocation in intestinal epithelial cells, and highlights the roles of internalization of tight-junction transmembrane proteins, as well as rearrangements of the cortical actin cytoskeleton, in intestinal inflammation.
Chiba
Hideki
H
Department of Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan. hidchiba@sapmed.ac.jp
Kojima
Takashi
T
Osanai
Makoto
M
Sawada
Norimasa
N
D000818:Animals; D018988:Bacterial Translocation / Q000502:physiology*; D002460:Cell Line; D004705:Endocytosis / Q000502:physiology*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000382:microbiology / Q000503:physiopathology*; D007371:Interferon-gamma / Q000502:physiology*; D008954:Models, Biological; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation; D010873:Pinocytosis / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D019108:Tight Junctions / Q000502:physiology*
D018994:Myosin Light Chains; D007371:Interferon-gamma