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

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....

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Bibliographic Details
Published in:PloS one 2012-03, Vol.7 (3), p.e32084
Main Authors: Laroui, Hamed, Ingersoll, Sarah A, Liu, Hong Chun, Baker, Mark T, Ayyadurai, Saravanan, Charania, Moiz A, Laroui, Famina, Yan, Yutao, Sitaraman, Shanthi V, Merlin, Didier
Format: Article
Language:English
Subjects:
Analysis
Analysis of Variance
Animals
Biology
Chains
Colitis - chemically induced
Colitis - metabolism
Colitis - pathology
Colon
Crohn's disease
Cytokines - blood
Cytoplasm
Dextran
Dextran Sulfate - adverse effects
Dextran Sulfate - metabolism
Dextrans
Diet, High-Fat
DNA Primers - genetics
Electric Impedance
Endoscopy, Gastrointestinal
Fatty acids
Fatty Acids - metabolism
Female
Histological Techniques
Inflammation
Inflammatory bowel disease
Inflammatory bowel diseases
Intestine
Linkages
Macromolecular Substances - metabolism
Medicine
Membranes
Mice
Mice, Inbred C57BL
Nanostructures - chemistry
Particle Size
Peroxidase - metabolism
Rodents
Signaling
Sodium
Sodium sulfate
Studies
Sulfates
Transport Vesicles - metabolism
Ulcerative colitis
Vesicles
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0032084