Interferon-γ induces internalization of epithelial tight junction proteins via a macropinocytosis-like process Matthias Bruewer * ,† ,1 , Markus Utech * ,† , Andrei I. Ivanov * , Ann M. Hopkins * , Charles A. Parkos * and Asma Nusrat * ,2 * 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 2 Correspondence: Department of Pathology and Laboratory Medicine, Emory University, Whitehead Research Building, Room 105E, 615 Michael St., Atlanta, GA 30322, USA. E-mail: anusrat@emory.edu Increased epithelial permeability is observed in inflammatory states. However, the mechanism by which inflammatory mediators such as IFN-γ increase epithelial permeability is unknown. We recently observed that IFN-γ 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-γ-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-γ-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-γ 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-γ induces internalization of epithelial tight junction proteins via a macropinocytosis-like process. Key Words: cytokines • inflammation • mucosa
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Interferon-γ induces internalization of epithelial tight junction proteins via a macropinocytosis-like process
Bruewer, Matthias; Utech, Markus; Ivanov, Andrei I.; Hopkins, Ann M.; Parkos, Charles A.; Nusrat, Asma
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, Volume 19 (8): 923
Fed of American Socs for Experimental Biology – Jun 1, 2005
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