Yasutada Akiba, Shin Nishii, Akinori Mizoguchi, Suguru Ito, Jonathan D Kaunitz
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引用次数: 0
Abstract
The entry of bacterial-derived lipopolysaccharides (LPS) from the intestinal lumen to the circulation induces low-grade systemic inflammation. We have found that LPS is transcellularly transported to the portal vein during luminal long-chain fatty acid (LCFA) exposure via CD36- and lipid raft-mediated pathways in rat jejunum, consistent with the involvement of caveolae-mediated endocytosis. We thus examined LPS transport in wild-type (WT) and caveolin-1 (Cav1) knockout (KO) murine jejunum. FITC-LPS was added to the mucosal bath of Ussing chambered muscle-stripped jejunal mucosa of WT and Cav1KO mice. Serosal appearance of FITC-LPS was measured with or without luminal application of oleic acid (OA, 10 mM) with taurocholic acid (TCA, 0.1 mM), or medium-chain fatty acid (MCFA) sodium caprate (C10, 30 mM). Luminal application of OA/TCA increased FITC-LPS m-to-s transport in WT jejunum, inhibited by the CD36 inhibitor sulfosuccinimidyl oleate or lipid raft inhibitor methyl-β-cyclodextrin, though not by the clathrin inhibitor chlorpromazine or Pitstop2, suggesting that LCFA-induced LPS transport is mediated by caveolae-mediated endocytosis. In contrast, OA/TCA-induced FITC-LPS transport was abolished in Cav1KO jejunum. Nevertheless, luminal C10 increased FITC-LPS transport in both WT and Cav1KO jejuna without transepithelial electrical resistance changes. Chlorpromazine and Pitstop2 inhibited C10-induced FITC-LPS transport, suggesting that C10 enhances transcellular LPS transport via clathrin-mediated endocytosis in the jejunum. These results suggest that LPS transport during LCFA exposure is mediated by Cav1-mediated endocytosis, whereas MCFA-induced LPS transport is via clathrin-mediated endocytosis. Modulation of epithelial endocytosis may be a new therapeutic target for the prevention of dietary lipid -associated endotoxemia, including the metabolic syndrome.
期刊介绍:
Tissue Barriers is the first international interdisciplinary journal that focuses on the architecture, biological roles and regulation of tissue barriers and intercellular junctions. We publish high quality peer-reviewed articles that cover a wide range of topics including structure and functions of the diverse and complex tissue barriers that occur across tissue and cell types, including the molecular composition and dynamics of polarized cell junctions and cell-cell interactions during normal homeostasis, injury and disease state. Tissue barrier formation in regenerative medicine and restoration of tissue and organ function is also of interest. Tissue Barriers publishes several categories of articles including: Original Research Papers, Short Communications, Technical Papers, Reviews, Perspectives and Commentaries, Hypothesis and Meeting Reports. Reviews and Perspectives/Commentaries will typically be invited. We also anticipate to publish special issues that are devoted to rapidly developing or controversial areas of research. Suggestions for topics are welcome. Tissue Barriers objectives: Promote interdisciplinary awareness and collaboration between researchers working with epithelial, epidermal and endothelial barriers and to build a broad and cohesive worldwide community of scientists interesting in this exciting field. Comprehend the enormous complexity of tissue barriers and map cross-talks and interactions between their different cellular and non-cellular components. Highlight the roles of tissue barrier dysfunctions in human diseases. Promote understanding and strategies for restoration of tissue barrier formation and function in regenerative medicine. Accelerate a search for pharmacological enhancers of tissue barriers as potential therapeutic agents. Understand and optimize drug delivery across epithelial and endothelial barriers.