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- Johansson, Malin E V, 1971, et al.
(författare)
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Bacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with ulcerative colitis.
- 2014
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 63:2, s. 281-291
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The inner mucus layer in mouse colon normally separates bacteria from the epithelium. Do humans have a similar inner mucus layer and are defects in this mucus layer a common denominator for spontaneous colitis in mice models and ulcerative colitis (UC)? METHODS AND RESULTS: The colon mucus layer from mice deficient in Muc2 mucin, Core 1 O-glycans, Tlr5, interleukin 10 (IL-10) and Slc9a3 (Nhe3) together with that from dextran sodium sulfate-treated mice was immunostained for Muc2, and bacterial localisation in the mucus was analysed. All murine colitis models revealed bacteria in contact with the epithelium. Additional analysis of the less inflamed IL-10(-/-) mice revealed a thicker mucus layer than wild-type, but the properties were different, as the inner mucus layer could be penetrated both by bacteria in vivo and by fluorescent beads the size of bacteria ex vivo. Clear separation between bacteria or fluorescent beads and the epithelium mediated by the inner mucus layer was also evident in normal human sigmoid colon biopsy samples. In contrast, mucus on colon biopsy specimens from patients with UC with acute inflammation was highly penetrable. Most patients with UC in remission had an impenetrable mucus layer similar to that of controls. CONCLUSIONS: Normal human sigmoid colon has an inner mucus layer that is impenetrable to bacteria. The colon mucus in animal models that spontaneously develop colitis and in patients with active UC allows bacteria to penetrate and reach the epithelium. Thus colon mucus properties can be modulated, and this suggests a novel model of UC pathophysiology.
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| 2. |
- Liu, Chang, et al.
(författare)
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NHE8 plays an important role in mucosal protection via its effect on bacterial adhesion.
- 2013
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Ingår i: American journal of physiology. Cell physiology. - : American Physiological Society. - 1522-1563 .- 0363-6143. ; 305:1
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Tidskriftsartikel (refereegranskat)abstract
- The Na(+)/H(+) exchanger NHE8 is expressed on the apical membrane of intestinal epithelial cells and is particularly abundant in the colon. Our previous study showed that Muc2 expression was significantly reduced in NHE8-knockout (NHE8(-/-)) mice, suggesting that NHE8 plays a role in mucosal protection in the colon. The current study confirms and extends our studies on the role of NHE8 in mucosal protection. The number of bacteria attached on the distal colon was significantly increased in NHE8(-/-) mice compared with their wild-type littermates. As expected, IL-4 expression was markedly increased in NHE8(-/-) mice compared with wild-type mice. Immunohistochemistry showed disorganization in the mucin layer of NHE8(-/-) mice, suggesting a possible direct bacteria-epithelia interaction. Furthermore, NHE8(-/-) mice were susceptible to dextran sodium sulfate-induced mucosal injury. In wild-type mice, dextran sodium sulfate treatment inhibited colonic NHE8 expression. In Caco-2 cells, the absence of NHE8 expression resulted in higher adhesion rates of Salmonella typhimurium but not Lactobacillus plantarum. Similarly, in vivo, S. typhimurium adhesion rate was increased in NHE8(-/-) mice compared with wild-type mice. Our study suggests that NHE8 plays important roles in protecting intestinal epithelia from infectious bacterial adherence.
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| 3. |
- Wang, Aiping, et al.
(författare)
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Loss of NHE8 expression impairs intestinal mucosal integrity
- 2015
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Ingår i: American Journal of Physiology - Gastrointestinal and Liver Physiology. - : American Physiological Society. - 0193-1857 .- 1522-1547. ; 309:11
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Tidskriftsartikel (refereegranskat)abstract
- The newest member of the Na(+)/H(+) exchanger (NHE) family, NHE8, is abundantly expressed at the apical membrane of the intestinal epithelia. We previously reported that mucin 2 expression was significantly decreased in the colon in NHE8(-/-) mice, suggesting that NHE8 is involved in intestinal mucosal protection. In this study, we further evaluated the role of NHE8 in intestinal epithelial protection after dextran sodium sulfate (DSS) challenge. Compared with wild-type mice, NHE8(-/-) mice have increased bacterial adhesion and inflammation, especially in the distal colon. NHE8(-/-) mice are also susceptible to DSS treatment. Real-time PCR detected a remarkable increase in the expression of IL-1β, IL-6, TNF-α, and IL-4 in DSS-treated NHE8(-/-) mice compared with DSS-treated wild-type littermates. Immunohistochemistry showed a disorganized epithelial layer in the colon of NHE8(-/-) mice. Periodic acid-Schiff staining showed a reduction in the number of mature goblet cells and the area of the goblet cell theca in NHE8(-/-) mice. Phyloxine/tartrazine staining revealed a decrease in functional Paneth cell population in the NHE8(-/-) small intestinal crypt. The expression of enteric defensins was also decreased in NHE8(-/-) mice. The reduced mucin production in goblet cells and antimicrobial peptides production in Paneth cells lead to disruption of the intestinal mucosa protection. Therefore, NHE8 may be involved in the establishment of intestinal mucosal integrity by regulating the functions of goblet and Paneth cells.
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