Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Elevated constitutive expression of major histocompatibility (MHC) class II antigens occurs in the enterocytes of patients with IBD. It has been suggested that this aberrant expression of class II molecules may play a role in the pathogenesis of IBD. We examined two possible reasons for such a finding. 1) Heightened sensitivity of IBD enterocytes to endogenous gamma interferon (gamma IFN) and 2) enhanced endogenous secretion of gamma interferon by intestinal cells in close proximity to the enterocytes (lamina propria lymphocytes). Constitutive and gamma interferon stimulated HLA-DR and DP density on intestinal epithelial cells (IEC) and peripheral blood monocytes (PBM) from UC patients (IEC n = 13; PBM n = 20), CD patients (IEC n = 14; PBM n = 18) and non-IBD controls (IEC n = 12; PBM n = 20) were measured via flow cytometry (mean channel fluorescence). gamma IFN production by PHA stimulated and unstimulated lamina propria lymphocyte (LPL) cultures of UC patients (n = 11) CD patients (n = 8) and non-IBD controls (n = 11) was measured using a vesicular stomatitis virus/WISH cell bioassay. We found significantly greater gamma IFN secretion by IBD-derived PHA stimulated LPL than from non-IBD stimulated controls (CD = 39.4 +/- 12.4u; UC41.5 +/- 6.8u; NL = 22.4 +/- 8.3u, p less than 0.05) while gamma IFN induced HLA-DR and DP upregulation was no greater in IBD-derived IEC and PBM than in non-IBD controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The expression and regulation of class II antigens in normal and inflammatory bowel disease peripheral blood monocytes and intestinal epithelium. 193 20

Colonic epithelial cells (CEC) were isolated from actively inflamed mucosa of IBD patients and checked for HLA-DR, HLA-DP, and HLA-DQ. Half of the freshly isolated CEC from IBD tissue expressed DR, and one third were positive for DP and DQ. Normal human CEC were then cultured for 24 h and their expression of these markers in response to different types of in vitro stimulation was investigated. A significant increase in the expression of DR, DP and DQ was observed in response to the nonspecific mitogen phytohaemagglutinin (PHA), the lymphokine gamma-interferon (gamma-IFN) and the epidermal growth factor (EGF). The enhancement of DR expression was more marked than that of DP and DQ. The effect of gamma-IFN was more rapid and significantly more marked than that of either PHA and EGF for all three antigens. EGF appeared to be more potent than PHA in enhancing the expression of DP and DQ. The data from this study indicate that HLA-D region antigens can be induced on human CEC by different types of stimuli and provide further evidence that the expression of these markers in the colonic epithelium is a normal event the magnitude of which can increase under various circumstances. The data also suggest that the increased expression of HLA-D region antigens by IBD CEC occurs as a result of different mechanisms, and that this expression is an indicator of the active participation of the colonic epithelium to the mucosal inflammatory response.
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PMID:HLA-D region antigens on isolated human colonic epithelial cells: enhanced expression in inflammatory bowel disease and in vitro induction by different stimuli. 314 53

The MHC status of epithelial cells from 32 primary colorectal neoplasms, villous adenomata (VA; 2) and inflammatory bowel disease (IBD; 3) were evaluated using a panel of monoclonal antibodies (mAbs). Class I antigens and beta 2 microglobulin (beta 2m) were expressed on all normal, benign, inflammatory and malignant epithelia with the exception of two carcinomas. A more complex pattern of reactivity was encountered with anti-class II mAbs. Some expression was detected on normal glandular and luminal epithelium, particularly adjacent to the tumour. Inflammatory tissues, VA and 23/32 carcinomas were also antigen-positive, the proportion of stained epithelial cells ranging from 5% to 90%. Expression was usually non-coordinate, DR being the predominant specificity followed by DP and DQ, which is suggestive of independent D region gene regulation. The hypothesis that class II expression is induced in vivo by locally generated IFN gamma was not confirmed by in vitro treatment with this agent of epithelial colorectal carcinoma-derived cell lines. These provisional data suggest that although IFN gamma may be a necessary stimulus for class II expression it is insufficient and that other factors also influence the responsiveness of tumour cells in this respect.
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PMID:Expression of MHC class II products on human colorectal cancer. An immunohistological and flow cytometric study. 346 76

We have described a murine model of IBD that was induced in C.B-17 scid mice by transfer of the CD45RBhi subpopulation of CD4+ T cells from normal BALB/c mice and could be prevented by cotransfer of the CD45RBlo CD4+ T cell subset. Here we have dissected the mechanism of pathogenesis of IBD in this model and used this information for rational immunotherapy of the disease. CD4+ cells from diseased mice displayed a highly polarized Th1 pattern of cytokine synthesis upon polyclonal stimulation in vitro. The administration of anti-IFN gamma MAb to mice soon after T cell transfer prevented development of colitis for up to 12 weeks. Continual neutralization of TNF with anti-TNF MAbs reduced the incidence of severe disease; however, neutralization of TNF during only the first 3-4 weeks had no effect. Severe colitis was completely abrogated in mice treated systemically with rIL-10, but not with rIL-4.
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PMID:Inhibition of Th1 responses prevents inflammatory bowel disease in scid mice reconstituted with CD45RBhi CD4+ T cells. 760 Feb 84

Inflammatory bowel diseases (IBD: Crohn's disease, ulcerative colitis) are chronic inflammatory and frequently relapsing diseases of the gut that ultimately lead to destruction of the intestinal tissue. Recent evidence suggests that a pathologic activation of the mucosal immune system in response to antigens is a key factor in the pathogenesis of IBD. Furthermore, changes in cell migration and cytokine production appear to contribute to the perpetuation of IBD and the postoperative recurrence of Crohn's disease. Based on recent advances in our understanding of the pathogenesis of IBD, several new therapeutic strategies are currently being tested in clinical practice, including recombinant anti-inflammatory cytokines (IFN-alpha, IL-10, IL-11) and inhibitors of cell adhesion molecules (ICAM), proinflammatory cytokines (TNF, IL-12) and their receptors (TNF, IL-6R).
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PMID:[Immunopathogenesis of inflammatory bowel diseases]. 1066 99

Cytokines are the key mediators of inflammation in the IBD and are focus of renewed interest to plan therapeutic strategies against this disease. However, there are gaps in our knowledge at present and a lot of questions need clear answers. Even with a therapy as specific as anti-TNF antibody, it is not clear if the benefit is attributable to simple binding and clearance of TNF-alpha or to binding on the cell surface and subsequent deletion of the activated macrophage. When a drug appears to be less effective than pre-clinical models suggest, can failures in effectiveness from delivery or dosing the differentiated? The disappointing results of clinical trials with IL-10 is at odds with the prediction of benefit from animal models. It even brings into question the validity of those models as well as the soundness of design of the clinical trials on which efficacy of IL-10 is assessed. Other exciting new methods to treat IBD could be use of monoclonal antibodies to effector T cell molecules (such as CD4 or CD44v7) removal of such cytokine secreting cells (apheresis), antibodies to proinflammatory cytokines (such as TNF-alpha, IFN-alpha, IFN-gamma, and IL-12) or administration of anti-inflammatory cytokines (such as IL-10, IL-11). Challenges in developing new therapeutic strategies include not only identifying novel agents, but also improving the definitions of clinical endpoints and defining efficacy at the biologic level. There is also need to further refine our knowledge about genetic elements and environment initiators to comprehensively manage IBD.
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PMID:Cytokines and inflammatory bowel disease. 1069 14

Intestinal epithelial cells seem to play a key role during IBD. The network of cellular interactions between epithelial cells and lamina propria mononuclear cells is still incompletely understood. In the following co-culture model we investigated the influence of intestinal epithelial cells on cytokine expression of T cytotoxic and T helper cells from patients with IBD and healthy controls. Peripheral blood mononuclear cells (PBMC) were purified by a Ficoll-Hypaque gradient followed by co-incubation with epithelial cells in multiwell cell culture insert plates in direct contact as well as separated by transwell filters. We used Caco-2 cells as well as freshly isolated colonic epithelia obtained from surgical specimens. Three-colour immunofluorescence flow cytometry was performed after collection, stimulation and staining of PBMC with anti-CD4, anti-CD8, anti-IFN-gamma and anti-IL-4. Patients with IBD (Crohn's disease (CD), n = 12; ulcerative colitis (UC), n = 16) and healthy controls (n = 10) were included in the study. After 24 h of co-incubation with Caco-2 cells we found a significant increase of IFN-gamma-producing CD8+ lymphocytes in patients with IBD. In contrast, healthy controls did not respond to the epithelial stimulus. No significant differences could be found between CD and UC or active and inactive disease. A significant increase of IFN-gamma+/CD8+ lymphocytes in patients with UC was also seen after direct co-incubation with primary cultures of colonic crypt cells. The observed epithelial-lymphocyte interaction seems to be MHC I-restricted. No significant epithelial cell-mediated effects on cytokine expression were detected in the PBMC CD4+ subsets. Patients with IBD-even in an inactive state of disease-exert an increased capacity for IFN-gamma induction in CD8+ lymphocytes mediated by intestinal epithelial cells. This mechanism may be important during chronic intestinal inflammation, as in the case of altered mucosal barrier function epithelial cells may become targets for IFN-gamma-producing CD8+ lymphocytes.
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PMID:Patients with inflammatory bowel disease (IBD) reveal increased induction capacity of intracellular interferon-gamma (IFN-gamma) in peripheral CD8+ lymphocytes co-cultured with intestinal epithelial cells. 1116 92

Using hematoxylin and eosin (H&E)-stained sections, Paneth cells are identified by the presence of eosinophilic granules. Several other methods have been proposed to stain Paneth cells. Recently, we noticed that Paneth cells were autofluorescent in H&E sections. To assess the number of Paneth cells by this method, 30 surgical specimens from the small bowel and 10 from the colon with IBD were investigated. Consecutive sections were stained with H&E and immunostained with lysozyme (Lz). Paneth cell counting was done in 20 well-oriented, vertically cut crypts per-case using alternatively transmitted light (TL) and incident-light fluorescence (ILF). When H&E and Lz sections were observed with TL, the number of Paneth cells was easily assessed in some crypts, but in crypts having numerous Paneth cells, their exact number was ascertainable. On the other hand, using IFL, the number of H&E-stained Paneth cells-crypt was easily assessed, even in crypts with Paneth cell clustering. Using H&E-ILF, a mean of 3.9 (range 3-8) Paneth cells-pe-crypt was found in the normal small bowel and a mean of 3.3 (range 1-14) in the colon with IBD. ILF provided the adequate visual conditions--i.e. a dark, non-autofluorescent background--for assessing the actual number of normal and metaplastic Paneth cells, even when arranged in tight cell groups. The present method will improve the enumeration of the actual number of normal and metaplastic Paneth cells both in experimental research and in clinical trials.
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PMID:A simple method to demonstrate normal and metaplastic Paneth cells in tissue sections. 1265 93

We previously found in Giemsa-stained colorectal sections from IBD patients that eosinophilic granulocytes turned fluorescent when excited with indirect fluorescent light, while other inflammatory cells were non-fluorescent. We now studied with that method, the frequency of eosinophilic granulocytes in sections from patients with eosinophilic esophagitis (EE). Cell counting was done in consecutive sections stained with Giemsa stain using indirect fluorescence light (G-IFL setting) and with hematoxylin-eosin using transmitted light (HE-TL setting) in 5 cases of EE and in 10 consecutive cases of reflux esophagitis (RE) grade 2. In EE 45.0 eosinophils/case (range 39-51) were recorded with the G-IFL setting but only 33.4 eosinophils/case (range 28-39) with the HE-TL setting (p < 0.05). In RE cases, 3 eosinophils/case (range 2-4) were found with the G-IFL setting and 2 eosinophil/case (range 1-3) with the HE-TL setting. The G-IFL method is not only more sensitive in detecting eosinophils than the conventional HE-TL method but also quicker, since a differential cell counting is not necessary.
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PMID:An improved method to visualize eosinophils in eosinophilic esophagitis. 1709 78

Infectious bursal disease virus (IBDV) is the causative agent of infectious bursal disease in chickens and causes a significant economic loss for the poultry industry. Little is understood about the mechanism involved in the host responses to IBDV infection. For better understanding the IBDV-host interaction, we measured steady-state levels of transcripts from 28 cellular genes of chicken embryo (CE) cell cultures infected with IBDV vaccine stain Bursine-2 during a 7-day infection course by use of the quantitative real-time RT-PCR SYBR green method. Of the genes tested, 21 genes (IRF-1, IFN 1-2 promoter, IFNAR-1, IRF-10, IFN-gamma, 2',5'-OAS, IAP-1, caspase 8, TRAIL-like, STAT-3, IL-6, IL-8, MIP-3 alpha, MHC-I, MHC-II, TVB, GLVR-1, OTF, IL-13R alpha, ST3GAL-VI and PGK) showed an increased expression. The remaining seven genes (IFNAR-2, IFN-alpha, NF-kappaB subunit p65, BLRcp38, DDX1, G6PDH and UB) showed a constant expression or only slight alteration. Apparently, the host genes involved in pro-inflammatory response and apoptosis, interferon-regulated proteins, and the cellular immune response were affected by IBDV infection, indicating involvement in the complex signaling pathways of host responses to the infection. This study thus contributes to the understanding of the pathogenesis of IBD and provides an insight into the virus-host interaction.
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PMID:Transcriptional profiles of chicken embryo cell cultures following infection with infectious bursal disease virus. 1714 81


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