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Author Notes:

Correspondence: hlaroui@gsu.edu

Conceived and designed the experiments: HL DM SVS. Performed the experiments: HL SAI SVS FL HL YY MAC. Analyzed the data: HL DM SVS. Contributed reagents/materials/analysis tools: HL DM SVS. Wrote the paper: HL DM. Proof read the manuscript: MB SA.

We dedicate this article to the memory of Dr. Shanthi V. Sitaraman, a brilliant scientist, dedicated physician, passionate humanitarian and dearest friend.

Subjects:

Research Funding:

This work was supported by grants from the Department of Veterans Affairs and the National Institutes of Health of Diabetes and Digestive and Kidney by RO1-DK-071594.

Keywords:

  • Analysis of Variance
  • Animals
  • Colitis
  • Cytokines
  • DNA Primers
  • Dextran Sulfate
  • Diet, High-Fat
  • Electric Impedance
  • Endoscopy, Gastrointestinal
  • Fatty Acids
  • Female
  • Histological Techniques
  • Macromolecular Substances
  • Mice
  • Mice, Inbred C57BL
  • Nanostructures
  • Particle Size
  • Peroxidase
  • Transport Vesicles

Dextran sodium sulfate (dss) induces colitis in mice by forming nano-lipocomplexes with medium-chain-length fatty acids in the colon

Tools:

Journal Title:

PLoS ONE

Volume:

Volume 7, Number 3

Publisher:

, Pages e32084-e32084

Type of Work:

Article | Final Publisher PDF

Abstract:

Inflammatory bowel diseases (IBDs), primarily ulcerative colitis and Crohn's disease, are inflammatory disorders caused by multiple factors. Research on IBD has often used the dextran sodium sulfate (DSS)-induced colitis mouse model. DSS induces in vivo but not in vitro intestinal inflammation. In addition, no DSS-associated molecule (free glucose, sodium sulfate solution, free dextran) induces in vitro or in vivo intestinal inflammation. We find that DSS but not dextran associated molecules established linkages with medium-chain-length fatty acids (MCFAs), such as dodecanoate, that are present in the colonic lumen. DSS complexed to MCFAs forms nanometer-sized vesicles ~200 nm in diameter that can fuse with colonocyte membranes. The arrival of nanometer-sized DSS/MCFA vesicles in the cytoplasm may activate intestinal inflammatory signaling pathways. We also show that the inflammatory activity of DSS is mediated by the dextran moieties. The deleterious effect of DSS is localized principally in the distal colon, therefore it will be important to chemically modify DSS to develop materials beneficial to the colon without affecting colon-targeting specificity. © 2012 Laroui et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Copyright information:

© 2012 Laroui et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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