Interferon-gamma induces internalization of epithelial tight junction proteins via a macropinocytosis-like process.


Increased epithelial permeability is observed in inflammatory states. However, the mechanism by which inflammatory mediators such as IFN-gamma increase epithelial permeability is unknown. We recently observed that IFN-gamma 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-gamma-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-gamma-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-gamma produces a leaky epithelial barrier by inducing macropinoytosis of TJ proteins.

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@article{Bruewer2005InterferongammaII, title={Interferon-gamma induces internalization of epithelial tight junction proteins via a macropinocytosis-like process.}, author={Matthias Bruewer and Markus Utech and Andrei I. Ivanov and Ann M. Hopkins and Charles A Parkos and Asma Nusrat}, journal={FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, year={2005}, volume={19 8}, pages={923-33} }