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)

In this study, the protective effect of Polygalae root was evaluated in a murine model of experimental colitis by intrarectal injection with 2,4,6-trinitrobenzene sulfonic acid (TNBS). Polygalae root, given orally at 2, 4 g/kg body weight of herbs once a day consecutively for 9 days, could recover the lost body weight and decrease the gross rectal bleeding. Polygalae root also reduced the degree of inflammation and improved significantly the histological changes such as infiltration by polymorphonuclear leukocytes and multiple erosive lesions. Furthermore, the cytokine production of intraepithelial lymphocytes was analyzed. The results showed that IFN-gamma was increased, but IL-4 was decreased in TNBS-induced colitis, when those were compared with the sham controls. But the administration of Polygalae root to TNBS-induced colitis mice showed lower production of IFN-gamma and higher production of IL-4 than the TNBS-induced colitis. These results suggest that the protective effects of Polygalae root against the TNBS colitis may be associated with the regulation of cytokine production of intraepithelial lymphocytes.
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PMID:Protective effects of Polygalae root in experimental TNBS-induced colitis in mice. 1184 39

The balance between pro and antiinflammatory cytokines secreted by T cells regulates both the initiation and perpetuation of inflammatory bowel diseases (IBD). In particular, the balance between interferon (IFN)-gamma/interleukin (IL)-4 and transforming growth factor (TGF)-beta activity controls chronic intestinal inflammation. However, the molecular pathways that evoke these responses are not well understood. Here, we describe a critical role for the transcription factor T-bet in controlling the mucosal cytokine balance and clinical disease. We studied the expression and function of T-bet in patients with IBD and in mucosal T cells in various T helper (Th)1- and Th2-mediated animal models of chronic intestinal inflammation by taking advantage of mice that lack T-bet and retroviral transduction techniques, respectively. Whereas retroviral transduction of T-bet in CD62L(+) CD4(+) T cells exacerbated colitis in reconstituted SCID mice, T-bet-deficient T cells failed to induce colitis in adoptive transfer experiments suggesting that overexpression of T-bet is essential and sufficient to promote Th1-mediated colitis in vivo. Furthermore, T-bet-deficient CD62L(-) CD4(+) T cells showed enhanced protective functions in Th1-mediated colitis and exhibited increased TGF-beta signaling suggesting that a T-bet driven pathway of T cell activation controls the intestinal balance between IFN-gamma/IL-4 and TGF-beta responses and the development of chronic intestinal inflammation in T cell-mediated colitis. Furthermore, TGF-beta was found to suppress T-bet expression suggesting a reciprocal relationship between TGF-beta and T-bet in mucosal T cells. In summary, our data suggest a key regulatory role of T-bet in the pathogenesis of T cell-mediated colitis. Specific targeting of this pathway may be a promising novel approach for the treatment of patients with Crohn's disease and other autoimmune diseases mediated by Th1 T lymphocytes.
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PMID:The transcription factor T-bet regulates mucosal T cell activation in experimental colitis and Crohn's disease. 1199 18

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

There is increasing evidence that interleukin (IL)-4 can aid in Th1-type inflammatory responses in chronic colitis models. In this study, we evaluated the effects of IL-4 and/or IL-17 on IL-6 secretion in human colonic myofibroblasts. IL-6 secretion was determined by ELISA and Northern blotting. IL-6 secretion was rapidly induced by either IL-4 or IL-17. IL-17 induced IL-6 mRNA expression within 1 h after stimulation, and reached a maximum at 3 h. IL-6 mRNA induction by IL-4 occurred more rapidly. A maximum induction of IL-6 mRNA by IL-4 was observed at 1 h after stimulation, and this was rapidly decreased. The combination of IL-4 plus IL-17 greatly enhanced IL-6 secretion and mRNA expression. In conclusion, IL-4, in particular IL-4 plus IL-17, induced IL-6 secretion in human colonic myofibroblasts. Th2 immune responses might play an important role in the pathogenesis of gut inflammation.
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PMID:Interleukin (IL)-4 and IL-17 synergistically stimulate IL-6 secretion in human colonic myofibroblasts. 1237 6

T lymphocytes expressing NK1.1 marker (NK1.1+) have been suggested as being important in peripheral immune modulation. Alteration of the balance between Th1 proinflammatory and Th2 anti-inflammatory cytokine-producing cells can ameliorate immune-mediated disorders. The aim of the study was to determine the role of NK1.1+ lymphocytes in the pathogenesis of tolerance and proinflammatory states and to determine their role in altering the Th1/Th2 balance in experimental colitis. Colitis was induced in C57/B6 mice by intracolonic instillation of trinitrobenzenesulfonic acid (TNBS). Mice received five oral doses of colonic proteins extracted from TNBS colitis colonic wall. Standard clinical, macroscopic, and microscopic scores were used for colitis assessment. Liver-associated lymphocytes and splenocytes were harvested 14 days following tolerance induction. Depletion of NK 1.1+ lymphocytes was performed 36 hr before lymphocyte harvesting. Lymphocytes were cultured for 12 hr with Con A and colitis extracted proteins. To evaluate the role of NK1.1+ lymphocytes in keeping a balance between immunogenic and tolerogenic subsets of cells, intracellular staining and flow cytometry assays were performed in tolerized and nontolerized mice. IL-4, IL-12, and IFN-gamma levels were measured by ELISA. Administration of mouse-derived colitis-extracted proteins ameliorated experimental colitis. Tolerized mice exhibited significant improvement in all macroscopic and microscopic parameters for colitis. Depletion of NK1.1 following tolerance induction significantly decreased the CD4(+)IL-4(+)/CD4(+)IFN-gamma(+) ratio in tolerized mice. However, depletion of NK1.1 lymphocytes in nontolerized mice increased the CD4(+)IL-4(+)/CD4(+)IFN-gamma(+) ratio, compared with nondepleted nontolerized mice. Induction of tolerance led to an increase in IL4 and a decrease in IFN-gamma levels. In the experimental colitis model NK1.1+ lymphocytes play a dual role: In the presence of peripheral tolerance they may be accountable for keeping the high CD4(+)IL-4(+)/CD4(+)IFN-gamma(+) ratio and disease alleviation. However, in nontolerized conditions they may induce a proinflammatory shift.
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PMID:NK 1.1+ T cell: a two-faced lymphocyte in immune modulation of the IL-4/IFN-gamma paradigm. 1240 60

Crohn's disease results from dysregulated T helper (Th)1-type mucosal inflammation. Crohn's disease is rare in tropical countries but prevalent in developed countries with temperate climates, in which its incidence rose after 1940. In contrast, exposure to helminthic parasites is common in tropical countries but is rare in developed countries. Helminthic parasites induce immunomodulatory T cell responses in the host. We hypothesize that immunomodulatory responses due to helminths may attenuate excessive Th1-type inflammation. To test that hypothesis, mice were exposed to eggs of the helminth Schistosoma mansoni and then challenged rectally with trinitrobenzesulfonic acid (TNBS) to induce colitis. Schistosome egg exposure attenuated TNBS colitis and protected mice from lethal inflammation. Schistosome egg exposure diminished IFN-gamma and enhanced IL-4 production from alphaCD3-stimulated spleen and mesenteric lymph node cells of TNBS-treated mice. Schistosome egg exposure decreased colonic IFN-gamma but increased IL-10 mRNA expression in TNBS-treated mice. Intact signal transducer and activator of transcription 6 was required for attenuation of colitis. Exposure to helminths can decrease murine colonic inflammation.
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PMID:Exposure to schistosome eggs protects mice from TNBS-induced colitis. 1243 3

We showed previously that cecal bacterial Ag (CBA)-specific CD4(+) T cells induce colitis when transferred into SCID mice. The purpose of this study was to generate and characterize CBA-specific regulatory T cells in C3H/HeJBir (Bir) mice. CD4(+) T cells were stimulated with CBA-pulsed APC in the presence of IL-10 every 10-14 days. After four or more cycles, these T cells produced high levels of IL-10, low levels of IL-4 and IFN-gamma, and no IL-2, consistent with the phenotype of T regulatory-1 (Tr1) cells. Bir Tr1 cells proliferated poorly, but their proliferation was dependent on CD28-B7 interactions and was MHC class II-restricted. Transfer of Bir Tr1 cells into SCID mice did not result in colitis, and cotransfer of Bir Tr1 T cells with pathogenic Bir CD4(+) Th1 cells prevented colitis. Bir Tr1 cells inhibited proliferation and IFN-gamma production of a CBA-specific Th1 cell line in vitro. Such inhibition was partly due to IL-10 and TGFbeta1, but cognate interactions with either APCs or Th1 cells were also involved. Normal intestinal lamina propria CD4(+) T cells had Tr1-like activity when stimulated with CBA-pulsed APCs. We conclude that CD4(+) T cells with the properties of Tr1 cells are present in the intestinal lamina propria and hypothesize that these cells maintain intestinal immune homeostasis to the enteric flora.
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PMID:Bacterial-reactive T regulatory cells inhibit pathogenic immune responses to the enteric flora. 1244 13

Epstein-Barr virus-induced gene 3 (EBI3) is a widely expressed IL-12p40-related protein that associates as a heterodimer with either IL-12p35 or an IL-12p35 homologue, p28, to create a new cytokine (IL-27). To define the function of EBI3 in vivo, we generated knockout mice in which the ebi3 gene was targeted by homologous recombination. EBI3-/- mice exhibited normal numbers of both naive and mature CD4+ and CD8+ T cells and B cells, but markedly decreased numbers of invariant natural killer T cells (iNKT) as defined by staining with an alpha-galactosylceramide (alphaGalCer)-loaded CD1d-tetramer. iNKT cells from EBI3-/- mice exhibited decreased IL-4 and, to a lesser extent, IFN-gamma production after alphaGalCer stimulation in vitro. A sustained decrease in IL-4 production was also observed in EBI3-/- mice after alphaGalCer stimulation in vivo in contrast to IFN-gamma production, which was only transiently decreased under such stimulation. Notably, EBI3-/- mice were resistant to the induction of immunopathology associated with oxazolone-induced colitis, a colitis model mediated primarily by T helper (Th) 2-type cytokine production by iNKT cells. In contrast, trinitrobenzene sulfonic acid-induced colitis, a predominantly Th1-mediated colitis model, was unaffected. Thus, EBI3 plays a critical regulatory role in the induction of Th2-type immune responses and the development of Th2-mediated tissue inflammation in vivo, which may be mediated through the control of iNKT cell function.
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PMID:Disruption of T helper 2-immune responses in Epstein-Barr virus-induced gene 3-deficient mice. 1248 40

Forbidden CD4(+)betabeta T cells, which produce interleukin (IL)-4 predominantly, are a pathological subset in the development of colitis in T-cell receptor alpha chain (TCRalpha)-deficient mice. Stimulation of naive CD4(+) T cells with IL-4 induces Th2 development via the activation of signal transducers and activators of transcription (STAT) 6. In the present study, we had found that IL-4 enhanced the expression of STAT6 in CD4(+)betabeta T cells isolated from TCRalpha(-/-) mice with colitis, suggesting that the IL-4 signal in the CD4(+)betabeta T cells is mediated by STAT6. To further investigate the role of STAT6 in the development of colitis induced by TCRalpha deficiency, we generated double-deficient mice by crossing TCRalpha(-/-) mice and STAT6(-/-) mice. Surprisingly, STAT6 deficiency did not result in decreased severity of colitis in TCRalpha(-/-) mice. STAT6-deficient CD4(+)betabeta T cells produced IL-4 and intraperitoneal injection of anti-IL-4 monoclonal antibody in the nondiseased TCRalpha(-/-) and STAT6 double-deficient mice prevented the colitis formation, thus indicating that the cells differentiated into the Th2 phenotype have the ability to mediate the development of the colitis in the absence of STAT6.
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PMID:Development of colitis in signal transducers and activators of transcription 6-deficient T-cell receptor alpha-deficient mice: a potential role of signal transducers and activators of transcription 6-independent interleukin-4 signaling for the generation of Th2-biased pathological CD4+ betabetaT cells. 1250 9

CD11c(+) (F4/80(-) CD68(-)) dendritic cells (DC) in the colonic lamina propria (cLP) of normal and immunodeficient (RAG1(-/-)) C57BL/6 (B6) mice show high surface expression of MHC class I/II molecules and CD1d, and low surface expression of CD40, CD80, CD86 costimulator molecules. CD4(+) alpha beta T cells from normal or MHC class II-deficient B6 mice transferred into congenic RAG1(-/-) hosts induce a progressive, lethal colitis. Concomitant with colitis development, DC in the inflamed cLP increase in number and up-regulate surface expression of CD1d, MHC class II molecules and CD40, CD80, CD86 costimulator molecules. cLP DC from non-transplanted (healthy) and transplanted (diseased) mice produce similar amounts of IL-12 p70 and IL-10 in response to CD40 signaling, but the inducible IL-12 p40 release is 5-15-fold higher in mice with colitis than in non-transplanted mice. Binding of IL-12 p40 to p19 generates IL-23. Freshly isolated cLP lymphocytes (cLPL) from transplanted, diseased mice express 3-10-fold more p19 transcripts than cLPL from non-transplanted, healthy mice. p19 expression by cLPL is further up-regulated in response to CD40 ligation. Freshly isolated cLP DC from transplanted mice with colitis (but not from non-transplanted controls) stimulate IFN-gamma (but not IL-4 or IL-13) release by co-cultured NKT cells. Incolitis, DC accumulate in the cLP, show an activated surface phenotype, up-regulate IL-12 p40 and p19 expression, and 'spontaneously' stimulate NKT-like cells. cLP DC may be interesting targets for novel therapeutic approaches to modulate mucosal T cell responses in situ.
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PMID:Colonic lamina propria dendritic cells in mice with CD4+ T cell-induced colitis. 1267 74


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