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induces internalization of epithelial tight junction proteins via a macropinocytosis-like process
,1
* Epithelial Pathobiology Research Unit, Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA; and
Department of General Surgery, University of Münster, Münster, Germany
2Correspondence: Department of Pathology and Laboratory Medicine, Emory University, Whitehead Research Building, Room 105E, 615 Michael St., Atlanta, GA 30322, USA. E-mail: anusrat{at}emory.edu
Increased epithelial permeability is observed in inflammatory states. However, the mechanism by which inflammatory mediators such as IFN-
increase epithelial permeability is unknown. We recently observed that IFN-
induces disassembly of tight junctions (TJ); in this study we asked whether such TJ disassembly is mediated by endocytosis of junctional proteins. The role of three major internalization pathways in disruption of TJ in IFN-
-treated intestinal epithelial cells was analyzed using selective inhibitors and markers of the pathways. No role for the clathrin- and caveolar-mediated endocytosis in the IFN-
-induced internalization of TJ proteins was observed. However, inhibitors of macropinocytosis blocked internalization of TJ proteins and junctional proteins colocalized with macropinocytosis markers, dextran and phosphatidylinositol-3,4,5-trisphosphate. Internalized TJ proteins were identified in early and recycling endosomes but not in late endosomes/lysosomes. These results for the first time suggest that IFN-
produces a leaky epithelial barrier by inducing macropinoytosis of TJ proteins.Bruewer, M., Utechm M., Ivanov, A. I., Hopkins, A. M., Parkos, C. A., Nusrat, A. Interferon-
induces internalization of epithelial tight junction proteins via a macropinocytosis-like process.
Key Words: cytokines inflammation mucosa
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