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)

pANCA (perinuclear antineutrophil cytoplasmic antibodies) occur at a high frequency in patients with ulcerative colitis. The purpose of this study was to investigate the frequency of pANCA in different mouse models of colitis and to determine whether there is any cross-reactivity of pANCA with bacterial antigens. Sera from 146 colitic mice and controls and from 30 patients with ulcerative colitis were tested for the presence of pANCA by indirect immunofluorescence with or without prior absorption with homogenized murine cecal bacteria. pANCA was found in 24 of 36 IL10(-/-) mice. In contrast to the human pANCA, both nuclear and perinuclear staining was found. Absorption of either human or mouse pANCA-positive sera with enteric bacterial antigens greatly reduced or abolished the specific perinuclear staining of pANCA. We conclude that pANCA occurs not only in humans but also in IL19(-/-) mice with colitis and likely represents a cross-reactivity with enteric bacterial antigens.
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PMID:pANCA represents a cross-reactivity to enteric bacterial antigens. 953 59

We sought to correlate the characteristic changes in goblet cell morphology in the chronically inflamed large intestine of 1L10-/- mice to specific changes in goblet cell gene expression. In healthy as well as IL10-/- mice, marked differences were found among the large intestinal regions in goblet cell morphology and gene expression. The mucin Muc2, which is a major determinant of goblet cell morphology, was expressed in most goblet cells, yet only in cells staining positive for both Alcian blue and high iron diamine. TFF3 was expressed in only a small subset of goblet cells. Inflamed colon of IL10-/- mice still contained high numbers of small, hypotrophic goblet cells with similar histochemical staining and Muc2 and TFF3 expression patterns, contradicting the often reported "goblet cell depletion" in colitis. Quantitatively, the Muc2 and TFF3 levels remained relatively stabile in IL10-/- mice. Muc2 in distal IL10-/- colon contained significantly less sulfate residues than in controls, which may compromise its protective properties.
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PMID:Fate of goblet cells in experimental colitis. 1239 2

The goal of this study was to evaluate for evidence of oxidative stress in colonic inflammation in a novel model of inflammatory bowel disease, nonsteroidal anti-inflammatory drug- (NSAID-) treated interleukin-10-deficient (IL10(-/-)) mice. IL10(-/-) and wild-type (wt) mice were treated with a nonselective NSAID (piroxicam, 200 ppm in the diet) for 2 weeks to induce colitis, and parameters for oxidative stress in the colonic tissues were evaluated. Mean chemiluminescence enhanced with lucigenin in the colons from IL10(-/-) mice treated with piroxicam was more than 5-fold higher than that of the control wt group. Chemiluminescence was inhibited with diphenylethylene iodinium, but not allopurinol, indomethacin, or N-omega-nitro-L-arginine, indicating that flavin-containing enzymes were the source of the reactive oxygen species. Colonic aconitase activity in NSAID-treated IL10(-/-) mice decreased to 50% of the activity of control mice. There was no difference in the total glutathione levels in the colonic mucosa among the groups; however, glutathione disulfide levels were approximately 2-fold greater in the colon of NSAID-treated IL10(-/-) mice as compared with control groups. Immunohistochemistry studies of colons from NSAID-treated IL10(-/-) mice demonstrated intense staining with two antibodies that recognize advanced glycation endproducts formed through glycation and oxidation: anticarboxymethylysine and antipentosidine. The epithelial cells and lamina propria cells in the colons of NSAID-treated IL10(-/-) mice showed immunostaining with antinitrotyrosine, indicating the presence of reactive nitrogen species. Colonic epithelium of IL10(-/-) mice with colitis showed moderate immunostaining for 8-hydroxy-2'-deoxyguanosine in the nuclei. NSAID-treated IL10(-/-) mice treated with diphenylene idodonium chloride (DPI), an irreversible inhibitor of flavoprotein enzymes, experienced significantly reduced inflammation. Taken together, these results strongly indicate the presence of oxidative stress in the inflammatory bowel disease in NSAID-treated IL10(-/-) mice and suggests a role for oxidative stress in the pathophysiology of this model of inflammatory bowel disease.
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PMID:Evidence for oxidative stress in NSAID-induced colitis in IL10-/- mice. 1270 96

Oral tolerance is the induction of immune hyporesponsiveness to orally administered antigens. It was described in association with a decrease in interferon gamma (IFNgamma) production by activated T cells. To determine the role of IFNgamma and IL10 in immunemodulation via oral tolerization. Colitis was induced by intracolonic instillation of trinitrobenzene sulfonic acid. Treated mice received five oral doses of colitis-extracted proteins (CEPs) every other day, starting immediately after colitis induction. Control mice received similar doses of bovine serum albumin. Colitis was assessed in both groups by standard clinical, micro- and macroscopic scores. IFNgamma and IL10 expression in splenic lymphocytes from both groups was tested by RT-PCR immediately after oral feeding, 1, 4, 8, 12, and 24 h thereafter and then every 24 h for 2 weeks. Feeding of CEPs markedly ameliorated experimental colitis. These mice gained weight and showed markedly improved macro- and microscopic parameters of colitis. Tolerized mice exhibited IFNgamma expression in splenic lymphocytes starting immediately following oral CEP immunization and up to 14 d thereafter. IL10 was expressed starting 1 h after CEP feeding and during the first 48 h thereafter. In contrast, non-tolerized control mice manifested IFNgamma expression starting on day 6 and had no IL10 expression. Early induction of IFNgamma expression by oral antigen may be associated with systemic tolerance in the experimental colitis setting. In contrast, late expression of IFNgamma is associated with a pro-inflammatory response in non-tolerized controls.
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PMID:Early expression of interferon gamma following oral antigen administration is associated with peripheral tolerance induction. 1285 Feb 7

Recent studies suggest that P-glycoprotein (Pgp) encoded by MDR1 gene, may be an important factor in the pathogenesis of inflammatory bowel disease (IBD). In this study, we investigated intestinal Pgp expression and activity: (1) in IL10 deficient (IL10(-/-)) mice which spontaneously develop intestinal inflammation affecting the small and large intestine and (2) in DSS (dextran sodium sulfate)-induced rat colitis. In IL10(-/-) enterocolitis mice, rhodamine 123 efflux was reduced by two to three-fold along the small and large intestine. This decrease was associated with a reduction in membrane's Pgp protein levels. A similar three-fold decrease in Pgps activity and expression was observed in the proximal colon in DSS-induced colitis in rats. However, in the non-inflamed ileum in DSS-induced rat colitis, epithelial cell's Pgp activity and protein levels were unexpectedly increased. This effect was specific to local inflammation since LPS induced systemic inflammation did affect neither the intestinal rho 123 efflux transport nor the abundance of the Pgp protein. These data demonstrate for the first time, an impaired function of epithelial Pgp in IL10 deficient enterocolitis mice. They also show an increase in Pgps activity in the non-inflamed ileum in the DSS-induced rat colitis, which may represent an adaptive mechanism to compensate the impaired activity of Pgp in the colon.
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PMID:Intestinal inflammation induces adaptation of P-glycoprotein expression and activity. 1588 61

Genetic deficiency in the expression of interleukin-10 (IL-10) is associated with the onset and progression of experimental inflammatory bowel disease (IBD). The clinical significance of IL-10 expression is supported by studies showing that immune-augmentation of IL-10 prevents inflammation and mucosal damage in animal models of colitis and in human colitis. Interleukin-10 (IL-10), an endogenous anti-inflammatory and immunomodulating cytokine, has been shown to prevent some inflammation and injury in animal and clinical studies, but the efficacy of IL-10 treatment remains unsatisfactory. We found that intra-peritoneal administration of adenoviral IL-10 to mice significantly reversed colitis induced by administration of 3% DSS (dextran sulfate), a common model of colitis. Adenoviral IL-10 (Ad-IL10) transfected mice developed high levels of IL-10 (394 +/- 136 pg/ml) within the peritoneal cavity where the adenovirus was expressed. Importantly, when given on day 4 (after the induction of colitis w/DSS), Ad-IL10 significantly reduced disease activity and weight loss and completely prevented histopathologic injury to the colon at day 10. Mechanistically, compared to Ad-null and DSS treated mice, Ad-IL10 and DSS-treated mice were able to suppress the expression of MAdCAM-1, an endothelial adhesion molecule associated with IBD. Our results suggest that Ad-IL10 (adenoviral IL-10) gene therapy of the intestine or peritoneum may be useful in the clinical treatment of IBD, since we demonstrated that this vector can reverse the course of an existing gut inflammation and markers of inflammation.
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PMID:Reversal of experimental colitis disease activity in mice following administration of an adenoviral IL-10 vector. 1625 32

Geographic and ethnic variations in ulcerative colitis and Crohn's disease frequency suggest that environmental factors affect disease risk. Prevention of parasitic worms (helminths) through improved hygiene may be one factor leading to the increased disease prevalence. Helminths alter host mucosal and systemic immunity. Animals exposed to helminths are protected from experimental colitis and other immunological diseases, and helminthic colonization can be used to treat ongoing murine and human disease. Helminths induce mucosal T cells to make Th2 and regulatory cytokines. Helminth-induced mucosal IL4, TGFbeta, and IL10 likely are part of the protective process. Helminths affect pathways of innate immunity like TLR4 expression and function. Worms also induce various regulatory-type T-cell subsets in the gut that limit effector T-cell growth and function. These effects of once ever-present helminths may have protected people from immune-mediated illnesses like inflammatory bowel disease.
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PMID:Helminths and mucosal immune modulation. 1705 16

The primary objective of this work is to determine the repairing potential of murine embryonic stem cells (ES) in murine model of Crohn's disease (CD). Colitis, induced in IL10-/- KO mice using piroxicam, was associated with the increased levels of IL-12. Enhanced yellow fluorescent protein (EYFP) marked murine ES cells (R1/129) and control non-fluorescent ES cells were subjected to in vitro differentiation into intestinal epithelial cells. IL 10-/- KO mice were injected with pre-differentiated ES-YFP cells and sacrificed after 2 and 3 months. Histopathological analysis of intestines demonstrated a progressive improvement in colitis (from grade-4 to grade-1 and -0) and decreased levels of IL-12 cytokine following transplantation. Fluorescent and confocal microscopy demonstrated presence of ES-EYFP cells in the colon, small intestine, liver, and thymus tissues but none in the spleen and bone marrow. The EYFP signal was not detected in sham (non-transplanted mice with induced colitis) and control IL10-/- KO mice. Engraftment, detected at 3 months post-transplant, correlated with markedly improved grading in colon histology (grade-1 or -0) and weight gain, as well as with decreased rectal prolapses. In vitro pre-differentiated ES cells migrated and homed exclusively into the colon, small intestine, and the liver, engrafted for long term, reduced inflammation and tissue damage, and restored immune balance. These findings suggest that pre-differentiated ES cells may become alternative source of stem cell therapy for CD with dual functions i.e. regenerating damaged epithelium and restoring immune imbalance occurring in this disease.
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PMID:Embryonic stem cells ameliorate piroxicam-induced colitis in IL10-/- KO mice. 1769 87

Chronic inflammation of mucosal surfaces renders them increasingly susceptible to epithelial cancers both in humans and mice. We have previously shown that anti-inflammatory CD4(+)CD45RB(lo)CD25(+) regulatory (Treg or T(R)) lymphocytes down-regulate inflammation and block development of bacteria-triggered colitis and colorectal cancer (CRC) in 129/SvEv Rag2-/- mice. Interestingly, T(R) cells collected from Interleukin (IL)-10-deficient cell donors not only failed to suppress carcinogenesis but instead promoted invasive mucinous colonic carcinoma with a strong gender bias expressing in male mice. We found we show that peritoneal invasion in this model is dependent on pleiotropic cytokine IL-6. Mucinous carcinoma arose rapidly and consistently after treatment with IL10-/- T(R) cells, which were found to express Foxp3+ and localize throughout tumor tissue. Carcinogenesis was rapidly reversible with transfer of wild type IL10-competent T(R) cells. Likewise, treatment with IL10-Ig fusion protein was sufficient to revert the lesions histologically, and restore inflammatory cytokine and oncogene expression to base line levels. These studies indicate an essential role for IL 6 in this CRC phenotype. Furthermore, immune-competent T(R) cells were important not only for preventing pathology but also for constructive remodeling of bowel following tumorigenic microbial insults. These data provide insights into etiopathogenesis of inflammation-associated epithelial invasion and maintenance of epithelial homeostasis.
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PMID:Rapid reversal of interleukin-6-dependent epithelial invasion in a mouse model of microbially induced colon carcinoma. 1772 75

Most mucosal surfaces of the mammalian body are colonized by microbial communities ("microbiota"). A high density of commensal microbiota inhabits the intestine and shields from infection ("colonization resistance"). The virulence strategies allowing enteropathogenic bacteria to successfully compete with the microbiota and overcome colonization resistance are poorly understood. Here, we investigated manipulation of the intestinal microbiota by the enteropathogenic bacterium Salmonella enterica subspecies 1 serovar Typhimurium (S. Tm) in a mouse colitis model: we found that inflammatory host responses induced by S. Tm changed microbiota composition and suppressed its growth. In contrast to wild-type S. Tm, an avirulent invGsseD mutant failing to trigger colitis was outcompeted by the microbiota. This competitive defect was reverted if inflammation was provided concomitantly by mixed infection with wild-type S. Tm or in mice (IL10(-/-), VILLIN-HA(CL4-CD8)) with inflammatory bowel disease. Thus, inflammation is necessary and sufficient for overcoming colonization resistance. This reveals a new concept in infectious disease: in contrast to current thinking, inflammation is not always detrimental for the pathogen. Triggering the host's immune defence can shift the balance between the protective microbiota and the pathogen in favour of the pathogen.
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PMID:Salmonella enterica serovar typhimurium exploits inflammation to compete with the intestinal microbiota. 1776 May 1


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