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- Title
Deoxynivalenol and E.coli lipopolysaccharide alter epithelial proliferation and spatial distribution of apical junction proteins along the small intestinal axis.
- Authors
Klunker, L. R.; Kahlert, S.; Panther, P.; Diesing, A. K.; Reinhardt, N.; Brosig, B.; Kersten, S.; Danicke, S.; Rothkotter, H. J.; Kluess, J. W.
- Abstract
We investigated a proposed syner-gistic effect of deoxynivalenol (DON) and lipo-polysaccharides (LPS) on small intestinal architec-ture and epithelial barrier integrity in pigs. Crypt depth and intestinal cell proliferation were ana-lyzed, as well as expression of zonula occludens protein-1 (ZO-1) and β-catenin of the apical junc-tion complex along the small intestine. Barrows (26.2 ± 4.1 kg) were fed restrictedly either a con-trol diet (CON) or a diet naturally contaminated with 3.1 mg DON/kg feed (DON) for 37 d. At d 37, the control group was infused for 1 h either with 100 µg/kg BW of DON (CON-DON, n = 6), 7.5 µg/kg BW of LPS (CON-LPS, n = 6), a combination of both (CON-DON+LPS, n = 7), or 0.9% NaCl (CON-CON, n = 6) and the DON group with 7.5 µg/kg BW of LPS (DON-LPS, n = 8) or 0.9% NaCl (DON-CON, n = 6). Pigs were euthanized 3.25 h after start of infusion. Immu-nohistochemistry (5'-bromo-2'-deoxyuridine for proliferation) and immunofluorescence (ZO-1 and P-catenin) from duodenum, proximal jejunum, mid-jejunum, proximal ileum, and terminal ileum were analyzed for crypt depth, cell proliferation, and apical junction proteins. Duodenal crypts were deeper compared with the other 4 intestinal regions, and proximal jejunal crypts were deeper than those of mid-jejunum and proximal ileum (P < 0.001). Epithelial proliferation showed a bell-shaped distribution along the small intestinal axis. Duodenal proliferating cells had the least number compared with jejunal sections and proximal ileum (P < 0.001). Neither DON nor LPS affected these variables. Zonula occludens-1 displayed a distinct spatial distribution in the epithelium with an api-cal and a cytosolic component. Apical expression of ZO-1 was severely damaged in the mid-jejunum (P < 0.001) of CON - DON compared with ani-mals treated with LPS. Also, in all animals receiv-ing LPS systemically, the cytosolic ZO-1 fraction in the 3 upper gut sections disappeared completely. This effect was independent of DON presence. Control pigs had a greater basolateral β-catenin accumulation (P < 0.05) in the cells, whereas the protein distribution did not differ in CON - DON pigs. In conclusion, results of this experiment dem-onstrated that epithelial proliferation has a distinct pattern along the small intestine and is not neces-sarily positively linked to crypt depth in pigs. Fur-thermore, results indicate that LPS changed the spatial distribution of ZO-1. A synergistic effect of DON and LPS on intestinal architecture could not be verified in the present study.
- Subjects
ESCHERICHIA coli; NIVALENOL; LIPOPOLYSACCHARIDES; EPITHELIAL cells; CELL proliferation; SMALL intestine
- Publication
Journal of Animal Science, 2013, Vol 91, Issue 1, p276
- ISSN
0021-8812
- Publication type
Article
- DOI
10.2527/jas.2012-5453