The reason for this might be that it was too large to easily diff

The reason for this might be that it was too large to easily diffuse into the mucus network. DSS and Dextran with a molecular mass of 40�C50 kDa, as normally used for the generation of DSS colitis can, however, penetrate the mucus quickly. DSS with all its sulfate groups are acidic in nature and one can speculate that the DSS effect on colon mucus could be similar to the pore forming effect of acid secreted from the stomach glands in the inner mucus layer covering the stomach epithelium [22]. The DSS sulfate groups might thus mimic the effect of hydrochloric acid in the stomach by opening pores in the colonic mucus. The normal approach for the generation of DSS colitis in rodents is to use 3 to 5% of DSS for 5�C7 days.

The DSS passes along the gastrointestinal tract without being degraded and the water absorption in the colon will probably give a higher concentration than that given in the drinking water. We chose to use 3% for both our in vivo and in-vitro experiments. However, still we could record the dramatic effects on the mucus. In the DSS colitis model, an overt inflammation is observed after 3�C5 days. The DSS effect observed here already after 12 h precedes inflammation and gives a relatively wide window during which the more typical colitis inflammation can develop. Studies of how the epithelial and immune systems are handling the bacteria during this time window should cast further light on the pathogenesis of colitis. The DSS effects on the epithelium has been associated with increased permeability and disruption of tight junctions, however epithelial barrier dysfunction alone is not sufficient to cause disease [23].

Disrupted epithelial junction barrier leading to inflammation also results in adherent bacteria on the epithelial surfaces [24]. During the short times of DSS exposure investigated here we explored if there were any toxic effects on the epithelium. Tissue sections revealed normal histology at 12 and 24 h. The epithelial cells had a normal function after 24 h of oral DSS administration as the tissue was able to secrete and generate a mucus layer with normal thickness. This mucus was secreted without being exposed to DSS, further supporting that the initial effects of DSS is on the mucus itself. The Muc2 mucin builds the structure of the mucus as it is the major component and has the biochemical properties in its oligomerized form to form net-like structures [8].

Analysis of the Muc2 mucin by gel electrophoresis and proteomics did not reveal any difference after 24 h of DSS intake. Thus we conclude that the epithelial cells seem to be functional and that they secrete a normal mucus layer after 24 h or less of DSS treatment. In mice with a thinner or no functional mucus layer, as for example germ-free mice, DSS treatment induces an acute and massive bleeding long before any inflammation is observed Carfilzomib [20], [25], [26].

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