Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009319 (colitis)
 19,384 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Colonic tissue obtained at surgery from control individuals and patients with ulcerative colitis was used to isolate mucins and to prepare mucin glycopolypeptides by pronase digestion. These were compared with mucins labelled with [35S] sulfate and [3H]-glucosamine after organ culture tissue samples from the same patients. A significant loss of mucin sulfation was detected in the colitis patients by both metabolic labelling and chemical analysis of the glycopolypeptides. A change in the size distribution of purified mucin oligosaccharides fractionated on BioGel P6 after release by beta-elimination was seen in both radiolabelled and non-labelled colitis mucins compared with controls. Amino acid analysis of the glycopolypeptides showed a close similarity to the expected ratio of serine:threonine:proline for MUC2 and did not vary between control and colitis groups. Analysis of the mucins confirmed > 90% purity in the labelling experiments, characteristic behaviour on density gradient centrifugation and agarose gel electrophoresis in control and ulcerative colitis groups and differences in sulfation and turnover at various sites in the normal colon.
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PMID:Colonic mucins in ulcerative colitis: evidence for loss of sulfation. 891 8

In the present study, we aimed to investigate enterocyte- and goblet cell-specific functions during the different phases of acute colitis induced with dextran sulfate sodium (DSS). Rats were treated with DSS for 7 days, followed by a 7-day recovery period. Colonic tissue was excised on days 2 (onset of disease), 7 (active disease), and 14 (regenerative phase). Enterocyte functions were studied by the expression of carbonic anhydrases (CAs), sodium/hydrogen exchangers (NHEs) and intestinal fatty acid-binding protein (iFABP) and by alkaline phosphatase (AP) activity. The expression and secretion of the mucin Muc2 and trefoil factor family peptide-3 (TFF3) were used as parameters for goblet cell function. DSS induced a downregulation of the CAs, NHEs, and iFABP in some normal-appearing surface enterocytes and in most of the flattened-surface enterocytes during disease onset and active disease. During the regenerative phase most enterocytes expressed these genes again. Quantitative analysis revealed a significant decrease in CAs, NHEs, and iFABP expression levels during onset and active disease. During the regenerative phase, the expression levels of the CAs were restored, whereas the expression levels of the NHEs and iFABP remained decreased. In contrast, enterocyte-specific AP activity was maintained in normal and flattened enterocytes during DSS-induced colitis. Goblet cells continued to express MUC2 and TFF3 during and after DSS treatment. Moreover, Muc2 and TFF3 expression and secretion levels were maintained or even increased during each of the DSS-induced disease phases. In conclusion, DSS-induced colitis was associated with decreased expression of CAs, NHEs, and iFABP. The loss of these genes possibly accounts for some of the pathology seen in colitis. The maintenance or upregulation of Muc2 and TFF3 synthesis and secretion levels implies that goblet cells at least maintain their epithelial defense and repair capacity during acute inflammation induced by DSS.
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PMID:Distinct epithelial responses in experimental colitis: implications for ion uptake and mucosal protection. 1206 4

We evaluated the small and large intestinal mucin production in a rat model of human ulcerative colitis by measuring the in vivo fractional synthesis rate (FSR) and the expression of mucins. A chronic colitis was induced by oral administration of 5% dextran sulfate sodium (DSS) for 9 days followed by 2% DSS for 18 days. DSS-treated rats showed increased colonic MUC2,3 mRNA levels compared pair-fed controls. The mucin FSR was unaffected while mucin-containing goblet cells were depleted in the vicinity of lesions. In the small intestine, no inflammatory lesions were observed but ileal MUC2 mRNA levels and mucin FSR were decreased by 46% and 21%, respectively. Finally, DSS-treated rats showed a marked decrease in mucin's threonine + serine content all along the gut, which may lead to a reduction of potential O-glycosylation sites. Our data indicate that the chronic colitis may impair the mucus layer protective function all along the gut.
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PMID:Mucin production and composition is altered in dextran sulfate sodium-induced colitis in rats. 1287 Jul 97

1. Diosmectite is a natural silicate effectively used in the treatment of infectious diarrhoea. Its antidiarrhoeal properties involve adsorption of toxins and bacteria and modifications of the rheological characteristics of gastrointestinal mucus. Hence, the aim of this study was to test the intestinal anti-inflammatory activity of diosmectite. 2. Diosmectite (500 mg x kg(-1) day(-1), p.o.) was administered as a post-treatment to rats with chronic trinitrobenzene sulphonic acid colitis. Colonic status was checked 1 and 2 weeks after colitis induction by macroscopic, histological and biochemical examination. 3. Diosmectite post-treatment resulted in amelioration of the morphological signs (intestinal weight, macroscopic damage, necrosed area, histology) and biochemical markers (myeloperoxidase activity, glutathione levels, MUC2 expression, inducible nitric oxide synthase and interleukin-1beta (IL-1beta) and leukotriene B(4) synthesis), as well as in the reduction of the severity of diarrhoea. The effect of the clay was comparable to that of sulphasalazine (50 mg x kg(-1) day(-1)). 4. 5. Diosmectite exhibited a dose-dependent capacity to adsorb proteins in vitro as well as a dose-dependent inhibitory effect on the basolateral secretion of IL-8 by lipopolysaccharide (LPS)-stimulated HT29 cells. Diosmectite had a dose-dependent inhibitory effect on IL-1beta production by LPS-stimulated THP-1 cells. 6. The effect of diosmectite on MUC2 was post-transcriptional, since mRNA levels were unaffected. However, diosmectite is able to upregulate MUC2 mRNA levels in HT29-MTX cells. 7. Diosmectite has anti-inflammatory activity administered as a post-treatment. Possible mechanisms include adsorption of luminal antigens, increase of colonic mucin levels and possibly a direct modulatory action of cytokine production by mucosal cells.
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PMID:Anti-inflammatory effect of diosmectite in hapten-induced colitis in the rat. 1499 5

HLA-B27 transgenic rats spontaneously developing a chronic inflammation mainly involving the colon are recognized as a powerful animal model for IBD. We investigated the mucin production in 6-month-old HLA-B27 rats by measuring in vivo fractional synthesis rate (FSR) and expression of mucins. In the inflamed colon of HLA-B27 rats, the mucin FSR was stimulated by 75% compared to F-344 controls, while MUC2,3 mRNA expression was unchanged. A local depletion in mucus-containing goblet cells was observed, suggesting a rapid mucin production/release and/or a real global decrease in goblet cell number. In the noninflamed jejunum of HLA-B27 rats, the mucin FSR was reduced by 35% compared to controls, while MUC2,3 mRNA expression was unchanged. Different alterations in mucin metabolism and expression are observed between HLA-B27 rats and a model of chemically induced chronic colitis (DSS-treated rats), suggesting that mucin alterations may be dependent on the animal model and colitis underlying mechanism.
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PMID:The chronic colitis developed by HLA-B27 transgenic rats is associated with altered in vivo mucin synthesis. 1510 81

Bile acids in the intestinal lumen contribute to the homeostatic regulation of proliferation and death of the colonic epithelial cells: Deoxycholic acid (DCA) appears to enhance and ursodeoxycholic acid (UDCA) to attenuate the process of chemically induced carcinogenesis. We studied the effects of UDCA on colitis-related colorectal carcinogenesis. Three groups of 25 mice were given 0.7% dextran sulphate in drinking water for 7 days and pure water for 10 days and were fed a standard diet containing double iron concentration. In 2 groups, the diet was supplemented with 0.2% cholic acid (CA), the precursor of DCA, or with 0.4% UDCA. After 15 cycles, the histology, the expression of MUC2, beta-catenin, p27 and p16 and the fecal water concentration of DCA and UDCA were investigated. All animals showed colitis with similar severity and histologic as well as immunophenotypic alterations, resembling those of human colitis. Among the animals fed the nonsupplemented diet, 46% developed colorectal adenocarcinomas and 54% anal-rectal squamous cell carcinomas. The prevalence of dysplasia and carcinomas did not change significantly in the animals given CA. Among the mice fed with UDCA, none developed adenocarcinomas and 20% squamous carcinomas. Dysplastic lesions were found in 88%, 67% and 40% of each group, respectively. The prevalence of dysplasia as well as of carcinoma showed an inverse relationship to the UDCA concentration in the fecal water. These data indicate that UDCA suppresses colitis-associated carcinogenesis. This model is suitable for investigation of the mechanism of the anticarcinogenic effect of UDCA in vivo.
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PMID:Prevention of colitis-associated carcinogenesis in a mouse model by diet supplementation with ursodeoxycholic acid. 1638 73

Chronic idiopathic inflammatory bowel disease (IBD) with extensive colonic involvement predisposes to the development of colorectal adenocarcinoma. Among the types of cancer occurring in this setting is an unusually well-differentiated low-grade tubuloglandular adenocarcinoma (LGTGA) that has not been studied systematically thus far. A review of 149 IBD-associated cancer resections performed at our institution yielded 17 patients (11%) with 21 tumors classified as LGTGA based on the following histologic characteristics: very well-differentiated small to medium diameter glands with round or tubular profiles, low-grade cytologic characteristics and absence or paucity of desmoplastic reaction. Twelve patients had ulcerative colitis, 4 Crohn disease, and 1 indeterminate colitis. Their median age was 41.5 years (range, 28 to 58 y). Five patients had separate synchronous cancers of conventional types. LGTGAs ranged from 0.4 to 10 cm in size and varied in gross appearance. They included 5 flat lesions that were not identified visually but were detected either by palpation of the unfixed surgical specimen (1 case) or histologically in random sections (4 cases). The invasive glands usually bore a close histologic resemblance to overlying low-grade or indefinite dysplastic crypts. Twelve carcinomas (57%) with well-defined superficial regions of LGTGA progressed histologically to conventional adenocarcinoma in deeper regions. These tumors were significantly more advanced than 9 carcinomas that maintained low-grade histology throughout. Follow-up of 13 patients (76%) for a mean 4.0 years (range, 0.75 to 9.0 y) disclosed 10 (77%) with favorable outcomes and 3 (23%) with adverse outcomes. Two adverse outcomes were attributable to synchronous advanced-stage conventional cancers and the third to progression from LGTGA to poorly differentiated adenocarcinoma. The mucosa overlying and surrounding LGTGA showed low-grade dysplasia (LGD) in 18 cases (86%), indefinite dysplasia with focal LGD in 1 case (5%), and LGD with focal high-grade dysplasia (HGD) in 2 cases (10%). Immunohistochemical studies disclosed expression of MUC2 in 72%, MUC6 in 0%, CK7 in 69%, and CK20 in 100%. Coexpression of CK7 and CK20 was conserved in regions of conventional adenocarcinoma derived from LGTGA. Silencing of immunohistochemical expression of hMLH1 occurred in 6 of 11 tumors tested (55%), implicating defective DNA replication error repair in their pathogenesis. We conclude that LGTGA is a distinct clinicopathologic entity characterized by direct derivation from LGD mucosa of IBD, very well-differentiated morphology, frequent coexpression of CK7 and CK20, and frequent silencing of hMLH1. Histologic progression from LGTGA to conventional types of adenocarcinoma parallels clinical progression to more aggressive neoplasia. The potential of LGD to give rise directly to LGTGA, and by way of LGTGA to more aggressive cancers, reinforces recommendations in favor of aggressive management of IBD patients diagnosed with LGD.
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PMID:Intestinal low-grade tubuloglandular adenocarcinoma in inflammatory bowel disease. 1686 75

Many studies dealing with trinitrobenzene sulfonic acid (TNBS) colitis in rats have been carried out referring only to the colon. In humans, ulcerative colitis (UC) can extend a variable distance into the terminal ileum in a phenomenon known as backwash ileitis (BWI). The aim of this study was therefore to examine the effect of TNBS-induced colitis on different aspects of the rat ileum and jejunum. We hypothesized that TNBS administration would lead to a systemic influence on the small intestine. Rats were induced colitis by administration of 0.25 ml of 2,4,6-trinitrobenzene sulfonic acid and 72 h after colitis induction animals were sacrificed. Segments were taken of the colon, ileum and jejunum. In addition to mucin mRNA expression, morphological changes were observed in the jejunum and ileum. We examined the mRNA expression and biochemical activity of brush border enzyme, sucrase iso-maltase and aminopeptidase, in all three segments. The villous surface area of colitis-induced rats was smaller in jejunum and ileum compared to control. In the jejunum of TNBS-induced rats, goblet-cell volume increased and their density decreased. The relative amount of MUC2 mRNA decreased in the jejunum, ileum and colon of colitis rat. However, MUC3 mRNA expression increased in the ileum and colon of these rats. Sucrase isomaltase expression and activity decreased in the ileum of TNBS-induced rats, while aminopeptidase activity was lower in the jejunum. These observations suggest that intrarectal administration of TNBS to rats influences not only their colon and terminal ileum, but also the proximal ileum and jejunum. Involvement of the ileum and jejunum in TNBS-induced colitis may be related to the systemic reaction of the immune system and mucosa to colitis.
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PMID:Mucosal function in rat jejunum and ileum is altered by induction of colitis. 1696 28

Cathelicidin, an antimicrobial peptide of the innate immune system, modulates microbial growth, wound healing, and inflammation. However, its association with inflammatory bowel diseases (IBDs) is unknown. Our objective was to determine whether cathelicidin would exert a modulatory effect on the progression of IBD and, if so, investigate the mechanism of action through which this effect occurred. We evaluated the potential for a synthetic cathelicidin, the mouse cathelin-related antimicrobial peptide (mCRAMP), to prevent the initiation and promote the healing of lesions from inflammatory colitis that was experimentally induced in mice with dextran sulfate sodium (DSS). During the experiment, mCRAMP was given: (i) as a parallel treatment starting together with 3% DSS feeding, and (ii) as a posttreatment starting 7 days after 3% DSS feeding. The body weight, fecal microflora populations, clinical symptoms, and histologic findings of colonic tissues were measured. Relative gene expression of mucins (MUC1, MUC2, MUC3, and MUC4) in colonic tissues was determined by real-time polymerase chain reaction. Intrarectal administration of mCRAMP ameliorated DSS-induced colitis with negligible effects on mucosal healing. The peptide also significantly reduced the increased number of fecal microflora in colitis animals. It reversed the decline of colonic mucus thickness during colitis through upregulation of the expression of mucin genes. Treatment with mCRAMP also prevented colitis development by suppressing the induction of apoptosis by DSS. The current study demonstrates for the first time that intrarectal administration of cathelicidin may be a novel therapeutic option for IBDs.
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PMID:A new role for cathelicidin in ulcerative colitis in mice. 1752 72

Expression of the mucin MUC2, the structural component of the colonic mucus layer, is lowered in ulcerative colitis. Furthermore, interleukin (IL)-10 knockout (IL-10-/-) mice develop colitis and have reduced Muc2 levels. Our aim was to obtain insight into the role of Muc2 and IL-10 in epithelial protection. Muc2-IL-10 double-knockout (Muc2/IL-10(DKO)) mice were characterized and compared to Muc2 knockout (Muc2-/-), IL-10-/- and wild-type (WT) mice. Clinical symptoms, intestinal morphology and differences in epithelial-specific protein levels were analyzed. In addition, levels of the pro-inflammatory cytokines in colonic tissue and serum were determined. IL-10-/- mice were indistinguishable from WT mice throughout this experiment and showed no clinical or histological signs of colitis. Muc2/IL-10(DKO) and Muc2-/- mice showed significant growth retardation and clinical signs of colitis at 4 and 5 weeks, respectively. Muc2/IL-10(DKO) mice had a high mortality rate (50% survival/5 weeks) compared to the other types of mice (100% survival). Microscopic analysis of the colon of Muc2/IL-10(DKO) mice showed mucosal thickening, increased proliferation, superficial erosions and a diminished Muc4 expression. Furthermore, pro-inflammatory cytokines were significantly upregulated, both in tissue (mRNA) and systemically in Muc2/IL-10(DKO) mice. In conclusion, Muc2/IL-10(DKO) mice develop colitis, which is more severe in every aspect compared to Muc2-/- and IL-10-/- mice. These data indicate that (i) in case of Muc2 deficiency, the anti-inflammatory cytokine IL-10 can control epithelial damage, though to a limited extent and (ii) the mucus layer is most likely a key factor determining colitis.
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PMID:Combined defects in epithelial and immunoregulatory factors exacerbate the pathogenesis of inflammation: mucin 2-interleukin 10-deficient mice. 1842 56


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