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. 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.

[1]  A. Venkatraman,et al.  Amelioration of dextran sulfate colitis by butyrate: role of heat shock protein 70 and NF-kappaB. , 2003, American journal of physiology. Gastrointestinal and liver physiology.

[2]  Didier Merlin,et al.  Nanomedicine in GI. , 2011, American journal of physiology. Gastrointestinal and liver physiology.

[3]  Jin-Ho Kim,et al.  Western‐style diets induce macrophage infiltration and contribute to colitis‐associated carcinogenesis , 2010, Journal of gastroenterology and hepatology.

[4]  A. Meager,et al.  Autoimmune polyendocrine syndrome type I in Slovakia: relevance of screening patients with autoimmune Addison's disease. , 2008, European journal of endocrinology.

[5]  R. Katori,et al.  Quantitation of left-to-right shunt from a single earpiece dye-dilution curve. , 1967, Journal of applied physiology.

[6]  M. J. Cody,et al.  Mice deficient in the CXCR2 ligand, CXCL1 (KC/GRO-α), exhibit increased susceptibility to dextran sodium sulfate (DSS)-induced colitis , 2008, Innate immunity.

[7]  A. Andoh,et al.  Physiological and anti-inflammatory roles of dietary fiber and butyrate in intestinal functions. , 1999, JPEN. Journal of parenteral and enteral nutrition.

[8]  Y. Kawashima,et al.  A pH-sensitive microsphere system for the colon delivery of tacrolimus containing nanoparticles. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[9]  A. Venkatraman,et al.  Increased permeability in dextran sulphate colitis in rats: time course of development and effect of butyrate. , 2000, Scandinavian journal of gastroenterology.

[10]  D. C. Cara,et al.  Oral administration of sodium butyrate attenuates inflammation and mucosal lesion in experimental acute ulcerative colitis. , 2012, The Journal of nutritional biochemistry.

[11]  L. G. Johnson,et al.  Enhanced epithelial gene transfer by modulation of tight junctions with sodium caprate. , 2000, American journal of respiratory cell and molecular biology.

[12]  J. Fellig,et al.  The inhibition of pancreatic ribonuclease by anionic polymers. , 1959, Archives of biochemistry and biophysics.

[13]  B. Reinhard,et al.  Control of colloid surface chemistry through matrix confinement: facile preparation of stable antibody functionalized silver nanoparticles. , 2010, ACS applied materials & interfaces.

[14]  M. Tomita,et al.  Absorption-enhancing mechanism of EDTA, caprate, and decanoylcarnitine in Caco-2 cells. , 1996, Journal of pharmaceutical sciences.

[15]  T. Sørensen,et al.  Familial occurrence of inflammatory bowel disease. , 1991, The New England journal of medicine.

[16]  S. Brant.  Update on the heritability of inflammatory bowel disease: the importance of twin studies. , 2011, Inflammatory bowel diseases.

[17]  Yutao Yan,et al.  ADAM-15 inhibits wound healing in human intestinal epithelial cell monolayers. , 2005, American journal of physiology. Gastrointestinal and liver physiology.

[18]  P. Artursson,et al.  Mechanism of Absorption Enhancement in Humans After Rectal Administration of Ampicillin in Suppositories Containing Sodium Caprate , 1997, Pharmaceutical Research.

[19]  T. Tamaoki,et al.  Interactions between dextran sulfate and Escherichia coli ribosomes. , 1967, Biochimica et biophysica acta.

[20]  F. Dal-Pizzol,et al.  N-acetylcysteine and deferoxamine reduce pulmonary oxidative stress and inflammation in rats after coal dust exposure. , 2005, Environmental research.

[21]  A. Bitton,et al.  Epidemiology of Crohn's Disease in QuéBec, Canada , 2009, Inflammatory bowel diseases.

[22]  Markus F. Neurath,et al.  Cytokines in inflammatory bowel disease , 2014, Nature Reviews Immunology.

[23]  R. Katori,et al.  Measurement of Bronchial Blood Flow in Tetralogy of Fallot , 1967, Circulation.

[24]  D. Aust,et al.  [Updated German guideline on diagnosis and treatment of ulcerative colitis, 2011]. , 2011, Zeitschrift fur Gastroenterologie.

[25]  M. Sata,et al.  Increased Circulating Concentrations of Growth-Related Oncogene (GRO)-α in Patients with Inflammatory Bowel Disease , 2006, Digestive Diseases and Sciences.

[26]  D. Granger,et al.  Impact of Dextran Sulfate Sodium Load on the Severity of Inflammation in Experimental Colitis , 2004, Digestive Diseases and Sciences.

[27]  P. Gillet,et al.  Hyaluronate-covered nanoparticles for the therapeutic targeting of cartilage. , 2007, Biomacromolecules.

[28]  Visualization of lumbar muscle contraction synergy using surface electromyography (sEMG) streaming topography , 2004, The 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[29]  P. Artursson,et al.  Mechanisms of absorption enhancement by medium chain fatty acids in intestinal epithelial Caco-2 cell monolayers. , 1995, The Journal of pharmacology and experimental therapeutics.

[30]  S. Kirk,et al.  Interleukin 10‐deficient colitis: new similarities to human inflammatory bowel disease , 2000, The British journal of surgery.

[31]  Riva G,et al.  Interreality: The Experiential Use of Technology in the Treatment of Obesity , 2011, Clinical practice and epidemiology in mental health : CP & EMH.

[32]  H. Cooper,et al.  Clinicopathologic study of dextran sulfate sodium experimental murine colitis. , 1993, Laboratory investigation; a journal of technical methods and pathology.

[33]  M. Tomita,et al.  Absorption-enhancing mechanism of sodium caprate and decanoylcarnitine in Caco-2 cells. , 1995, The Journal of pharmacology and experimental therapeutics.

[34]  W. Fiers,et al.  Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. , 2000, Science.

[35]  G. Dalmasso,et al.  Temporal and Spatial Analysis of Clinical and Molecular Parameters in Dextran Sodium Sulfate Induced Colitis , 2009, PloS one.

[36]  L. Philipson,et al.  THE PRESENCE OF DNA IN HUMAN ERYTHROCYTE MEMBRANES. , 1964, Biochimica et biophysica acta.

[37]  G. Tóth,et al.  Stabilization of local structures by pi-CH and aromatic-backbone amide interactions involving prolyl and aromatic residues. , 2001, Protein engineering.

[38]  G. Dalmasso,et al.  Drug-loaded nanoparticles targeted to the colon with polysaccharide hydrogel reduce colitis in a mouse model. , 2010, Gastroenterology.

[39]  D. Walsh,et al.  Tachykinins and the cardiovascular system. , 2006, Current drug targets.

[40]  G. Dalmasso,et al.  Functional TNFα gene silencing mediated by polyethyleneimine/TNFα siRNA nanocomplexes in inflamed colon. , 2011, Biomaterials.

[41]  O. Habler,et al.  Recombinant human interleukin-10 attenuates TNFalpha production by porcine monocytes. , 1998, European journal of medical research.

[42]  D. Hommes,et al.  Comparative analysis of colonic gene expression of three experimental colitis models mimicking inflammatory bowel disease , 2007, Inflammatory bowel diseases.

[43]  D. Merlin,et al.  Nanoparticle‐based therapeutic delivery of prohibitin to the colonic epithelial cells ameliorates acute murine colitis , 2011, Inflammatory bowel diseases.

[44]  J. Trotter,et al.  Immunosuppression and hepatocellular carcinoma , 2011, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.