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)

The therapeutic effects of tryptanthrin (TRYP), a natural product from the medicinal plant Polygonum tinctorium, were examined in a murine model of inflammatory bowel disease (IBD). Colitis was induced by 5% dextran sodium sulfate (DSS) in drinking water for 7 days from day 0. TRYP (100 mg/kg) was administered orally suspended in 5% arabia gum everyday from day 3 for 5 days. Histopathological analysis showed reduced colon damage in TRYP-treated mice on day 6; however, colon injury resumed after treatment was stopped. The production of prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) by untreated and treated mouse colon tissues cultured in vitro were mostly unchanged by TRYP treatment. However, mitogen-stimulated spleen cells from TRYP-treated colitic mice produced less interleukin 2 (IL-2) and less interferon-gamma (IFN-gamma) than untreated colitic mouse spleen cells, early after induction of colitis. When colitis was induced with 5% DSS for 7 days and TRYP was given to the mice for 8 days from day 3, TRYP enhanced the survival of the mice but results were not significant. A significant reduction of weight loss was observed in TRYP-treated mice with colitis induced by 5% DSS for 4 days as compared to control mice. Remarkably, whereas 90% of the vehicle-treated mice died from wasting disease, all the TRYP-treated mice survived, suggesting that TRYP may have a therapeutic effect on colitis.
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PMID:The natural plant product tryptanthrin ameliorates dextran sodium sulfate-induced colitis in mice. 1196 35

Nuclear factor-kappaB (NF-kappaB)-dependent up-regulation of inflammatory cytokines and inducible nitric oxide (iNOS) occurs in inflammatory bowel disease. We investigated the effect of alpha-phenylN-tert-butylnitrone (PBN), a spin-trapping agent that inhibits NF-kappaB activity, on dextran sulfate sodium (DSS)-induced colonic mucosal injury and inflammation in mice. Acute colitis was induced with DSS in female BALB/c mice receiving 0, 0.3, 3, and 30 mg/kg i.p. PBN daily. Colonic mucosal inflammation was evaluated biochemically and histologically. Nitric oxide was evaluated as luminal nitrite/nitrite concentration by the Griess reaction and as immunoreactive nitrotyrosine in mucosal cells. Mucosal tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were determined by immunoassay. Colonic mRNA expression for iNOS, TNF-alpha, and IFN-gamma was measured by reverse transcription-polymerase chain reaction, and NF-kappaB activation was evaluated by electrophoretic mobility shift assay. After DSS administration, mice showed increased luminal nitrite/nitrate, mucosal TNF-alpha and IFN-gamma, and mRNA for iNOS and these cytokines, in addition to decreased colonic length and increased inflammatory score, luminal hemoglobin, and colonic myeloperoxidase activity. PBN inhibited increases in luminal nitric oxide production, nitrotyrosine immunoreactivity, and mucosal TNF-alpha and IFN-gamma. Colonic iNOS, TNF-alpha, and IFN-gamma mRNA were suppressed by PBN, as was a DSS-induced increase in colonic NF-kappaB DNA-binding activity. NF-kappaB is essential to DSS-induced colitis, suggesting molecular approach targeting of NF-kappaB for treatment of inflammatory bowel disease.
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PMID:alpha-Phenyl-N-tert-butylnitrone provides protection from dextran sulfate sodium-induced colitis in mice. 1197 Aug 53

The objective of this study was to evaluate the expression of the immunoregulatory and pro-inflammatory cytokines interleukin (IL)-2, IL-4, IL-6, IL-12p35, IL-12p40, interferon-gamma (IFN-gamma), and tumour necrosis factor-alpha (TNF-alpha), and the expression of the predominantly immunosuppressive cytokines transforming growth factor-beta (TGF-beta) and IL-10 in canine idiopathic lymphocytic-plasmacytic colitis (LPC). Semi-quantitative reverse transcriptase-polymerase chain reactions were performed using specific primers on RNA isolated from the colonic mucosa of healthy dogs, dogs with clinical signs of large intestinal disease but normal histopathology of the colon, and dogs with LPC. Canine LPC was associated with over-expression of IL-2 compared to healthy colonic mucosa (p<0.01) and the mucosa of dogs with large intestinal diarrhoea but normal histopathology (p<0.05). Higher levels of TNF-alpha mRNA were also seen in LPC compared to healthy mucosa (p<0.05). These results indicate that LPC is associated with activation of CD4+ T-helper lymphocytes and increased production of T-helper-1-type cytokines.
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PMID:Evaluation of Th1, Th2 and immunosuppressive cytokine mRNA expression within the colonic mucosa of dogs with idiopathic lymphocytic-plasmacytic colitis. 1200 86

The association between oral contraceptives or pregnancy and inflammatory bowel disease is unclear. We investigated whether 17beta-estradiol modulates intestinal inflammation in two models of colitis. Female mice were treated with 17beta-estradiol alone or with tamoxifen, tamoxifen alone, 17 alpha-estradiol, or placebo. Dinitrobenzene sulfonic acid (DNB)- or dextran sodium sulfate (DSS)-induced colitis were assessed macroscopically, histologically, and by myeloperoxidase (MPO) activity. Malondialdehyde and mRNA levels of intercellular adhesion molecule-1 (ICAM-1), interferon-gamma (IFN-gamma), and interleukin-13 (IL-13) were determined. In DNB colitis, 17beta-estradiol alone, but not 17beta-estradiol plus tamoxifen, or 17 alpha-estradiol reduced macroscopic and histological scores, MPO activity and malondialdehyde levels. 17beta-Estradiol also decreased the expression of ICAM-1, IFN-gamma, and IL-13 mRNA levels compared with placebo. In contrast, 17beta-Estradiol increased the macroscopic and histological scores compared with placebo in mice with DSS colitis. These results demonstrate anti-inflammatory and proinflammatory effects of 17beta-estradiol in two different models of experimental colitis. The net modulatory effect most likely reflects a combination of estrogen receptor-mediated effects and antioxidant activity and may explain, in part, conflicting results from clinical trials.
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PMID:Modulatory effects of estrogen in two murine models of experimental colitis. 1206 88

Excessive intake of saturated fatty acids and/or linoleic acid favors the induction of an array of lipid mediators and cytokines enhancing inflammatory responses. Conversely, dietary supplementation with (n-3) fatty acids or vitamin D ameliorates inflammation and autoimmune diseases. Although it was well accepted that conjugated linoleic acid (CLA) prevented diseases with a common inflammatory pathogenesis (i.e., cancer and atherosclerosis), no studies were available on the roles of CLA in mucosal inflammation. The present study was designed to investigate the anti-inflammatory actions and molecular mechanisms underlying the regulation of colonic health by CLA. We hypothesized that colonic inflammation can be ameliorated by dietary CLA supplementation. To test this hypothesis, inflammation of the colonic mucosa was triggered by challenging pigs fed either soybean oil-supplemented or CLA-supplemented diets with an enteric bacterial pathogen (i.e., Brachyspira hyodysenteriae). Immunoregulatory cytokines and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) mRNA expression were assayed in colonic lymph nodes and colon of pigs. Colonic mucosal lesions and lymphocyte subset distribution were evaluated by histology and immunohistochemistry. Supplementation of CLA in the diet before the induction of colitis decreased mucosal damage; maintained cytokine profiles (i.e., interferon-gamma and interleukin-10) and lymphocyte subset distributions (i.e., CD4+ and CD8+), resembling those of noninfected pigs; enhanced colonic expression of PPAR-gamma; and attenuated growth failure. Therefore, CLA fed preventively before the onset of enteric disease attenuated inflammatory lesion development and growth failure.
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PMID:Nutritional regulation of porcine bacterial-induced colitis by conjugated linoleic acid. 1209 86

We have previously demonstrated that interleukin (IL)-10-deficient (IL-10 knockout [KO]) but not wild-type (WT) mice develop colitis after infection with Helicobacter hepaticus. Here, we show that infected recombination activating gene (RAG) KO mice develop intestinal inflammation after reconstitution with CD4(+) T cells from IL-10 KO animals and that the cotransfer of CD4(+) T cells from H. hepaticus-infected but not uninfected WT mice prevents this colitis. The disease-protective WT CD4(+) cells are contained within the CD45RB(low) fraction and unexpectedly were found in both the CD25(+) and the CD25(-) subpopulations of these cells, their frequency being higher in the latter. The mechanism by which CD25(+) and CD25(-) CD45RB(low) CD4(+) cells block colitis involves IL-10 and not transforming growth factor (TGF)-beta, as treatment with anti-IL-10R but not anti-TGF-beta monoclonal antibody abrogated their protective effect. In vitro, CD45RB(low) CD4(+) cells from infected WT mice were shown to produce IL-10 and suppress interferon-gamma production by IL-10 KO CD4(+) cells in an H. hepaticus antigen-specific manner. Together, our data support the concept that H. hepaticus infection results in the induction in WT mice of regulatory T cells that prevent bacteria-induced colitis. The induction of such cells in response to gut flora may be a mechanism protecting normal individuals against inflammatory bowel disease.
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PMID:Bacteria-triggered CD4(+) T regulatory cells suppress Helicobacter hepaticus-induced colitis. 1218 42

Peroxisome proliferator-activated receptor gamma (PPARgamma), a member of a nuclear transcription factor family, has been previously demonstrated to have antiinflammatory activity. The effects of PPARgamma activation in the development of an immune response are less well characterized. Through evaluation of PPARgamma heterozygote mice (PPARgamma(+/-) and specific PPARgamma agonist ligand binding, we evaluated the immunologic effects of PPARgamma activation in a well-described model of colitis. Increased susceptibility to dextran sodium sulfate (DSS)-induced colitis as defined by body weights, histologic injury, and survival was observed in the PPARgamma(+/-) mice in comparison to wild-type mice. Three different PPARgamma ligands (troglitazone, pioglitazone, and rosiglitazone) demonstrated beneficial dose-related treatment effects when administered prior to the onset of colitis. However, no protection was observed when PPARgamma ligand activation occurred after the onset of colitis. The reduction in DSS-induced inflammation noted with PPARgamma ligand treatment was associated with decreased interferon-gamma and tumor necrosis factor-alpha and increased interleukin (IL)-4 and IL- 10 levels as assessed by quantitative reverse transcriptase-polymerase chain reaction. Consistent with this shift towards a T helper (Th2) cytokine dominance, PPARgamma ligand treatment stimulated increased GATA-3 expression. These results indicate that the protective effects exhibited by PPARgamma ligands in intestinal inflammation may be due to immune deviation away from Th1 and towards Th2 cytokine production.
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PMID:Peroxisome proliferator-activated receptor gamma agonist ligands stimulate a Th2 cytokine response and prevent acute colitis. 1247 48

Tumor necrosis factor-alpha (TNF-alpha) is a key cytokine involved in the pathogenesis of inflammatory bowel disease. We have developed a second-generation antisense oligonucleotide (ISIS 25302) specific for murine TNF-alpha and have evaluated this oligonucleotide in two models of gut inflammation of distinct etiology. ISIS 25302 decreased TNF-alpha mRNA in a dose- and sequence-dependent manner in vitro in the mouse macrophage cell line P388D1. It also reduced TNF-alpha mRNA in vivo, in whole adipose tissue and in macrophages isolated from the adipose tissue of db/db mice, a strain with constitutively high expression of TNF-alpha. ISIS 25302 significantly reduced disease activity index scores in mice with both an acute and a chronic form of dextran sodium sulfate (DSS)-induced colitis. It also significantly improved histopathological scores in interleukin (IL)-10-deficient mice. This was accompanied by reductions in both the basal and lipopolysaccharide-stimulated secretion of TNF-alpha and interferon-gamma in colonic organ cultures from IL-10 -/- mice. In this model, efficacy was obtained with both a prophylactic treatment regimen or a therapeutic dosing protocol begun after colitis was already present. In both the DSS and IL-10 -/- models, scrambled and mismatch control oligonucleotides were largely without effect, suggesting that ISIS 25302 was exerting its effects through a sequence-dependent antisense mechanism.
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PMID:Antisense oligonucleotide blockade of tumor necrosis factor-alpha in two murine models of colitis. 1249 Jun 18

Interleukin (IL)-18 is a cytokine with a broad array of effector functions, the most prominent of which is to act synergistically with IL-12 in interferon-gamma production and the induction of a strong T-helper-1-mediated immune response. In addition, IL-18 also upregulates the production of proinflammatory cytokines such as IL-1 and tumor necrosis factor-alpha. Analysis of IL-18-deficient mice revealed an important role of IL-18 in the activation of macrophages and natural killer cells in the context of infection with intracellular bacteria or parasites. In humans, it was reported that IL-18 is elevated at sites of inflammation in inflammatory bowel disease (IBD), particularly in Crohn's disease, suggesting a possible role for IL-18 in the development and persistence of IBD. In this review we summarize recent findings on the functional role of IL-18 in the pathogenesis of colitis with a special focus on murine models of IBD. The neutralizing mouse anti-mouse IL-18 antibodies generated in our group should facilitate the evaluation of the efficiency of therapeutic blockade of endogenous IL-18 in chronic mouse models of colitis besides the use of recombinant forms of the inhibitory IL-18-binding protein.
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PMID:Anti-interleukin-18 therapy in murine models of inflammatory bowel disease. 1257 21

We developed two kinds of delivery systems targeting mucosal immune regulating cells with poly (D,L-lactic acid) microspheres containing dexamethasone and dichloromethylene diphosphonate, and gelatine microspheres containing interleukin-10. To estimate the efficacy of these drug delivery systems, we studied the effects on experimental colitis induced by dextran sodium sulfate, 2,4,6-trinitrobenzene sulfonic acid, and interleukin-10-deficient mice. Intestinal administration of these microspheres significantly improved colitis with decreased histological score, myeloperoxidase activity, and nitric oxide production compared with mice treated with free agents. Gene expressions of tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma were down-regulated in treated animals. Serum Dx, IL-10 levels, and systemic macrophages were unchanged after treatment. Our findings suggest that local macrophages in the intestine play a critical role in the initiation of chronic colitis in the animal model of inflammatory bowel disease (IBD). Intestinal drug delivery systems with biodegradable microspheres targeting mucosal immune-regulating cells may become a therapeutic approach to human IBD.
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PMID:Intestinal drug delivery systems with biodegradable microspheres targeting mucosal immune-regulating cells for chronic inflammatory colitis. 1257 65


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