Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007570 (celiac disease)
 13,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokines are important mediators of the inflammatory reaction and microvascular injury after trauma and tissue ischemia. The plasma activity of a cytokine reflects the net effect of positive and negative signals. We examined the sequential serum activity of IL-1, IL-2, IL-6, and TNF in a severe model of splanchnic artery occlusion (SAO) shock induced in rats by total occlusion of the superior mesenteric and the celiac arteries for 40 min. A control group with negligible surgical intervention and two sham-shock groups, one with minor operation and another with major surgery employed in SAO rats, both without vascular occlusion, were also studied. No IL-1 activity was detected throughout the 190-min experimental protocol in any of the groups. Low activity of IL-2 was measured only in SAO rats (approximately 1 U/ml at the peak). We found graded increases in serum TNF and IL-6 activities which were proportional to the surgical trauma and were highest in SAO rats (IL-6 up to 30 U/ml, P less than 0.01 from both sham groups; TNF, 2500 pg/ml 30 min after reperfusion, P less than 0.01 from both sham groups). These data further support the role played by cytokines in the early mediation of surgical trauma and shock.
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PMID:Acute release of cytokines is proportional to tissue injury induced by surgical trauma and shock in rats. 191 66

Human intestinal lamina propria T cells have a low expression of the CD45RA antigen and a high expression of the CD45RO antigen. This phenotype is characteristic for memory T cells. In addition, T cells in the effector compartment of the mucosa bear surface antigens that are very rarely found in other sites of the immune system. Intestinal T cells also express functional IL-2 receptors, and IL-2 receptor alpha-chain mRNA, and are able to synthesize high amounts of IL-2. However, other markers of memory T cells, as CD29, are not expressed in high density in the lamina propria, indicating that lamina propria T cells differ from "classical" memory T cells. This is supported by functional studies in nonhuman primates infected rectally with Chlamydia trachomatis that show that lamina propria T cells do not proliferate after stimulation with antigen but rather provide helper function for immunoglobulin synthesis. These findings indicate a specific state of differentiation of lamina propria T cells that is adapted to the specific requirements in the gut. In inflammatory bowel disease (IBD) and in celiac disease, an increase in the number of CD25-positive activated T cells is found in involved mucosa. It has been shown that mucosal T-cell activation induces epithelial cell damage and mucosal transformation. Thus, a T cell-mediated damage may contribute to the pathogenesis of IBD. HIV-infected patients have a decreased number of CD4-positive T cells in the intestinal lamina propria. The number of CD25-positive activated T cells is also significantly decreased in the intestine compared to controls. Correlating with the presence of HIV-infected mononuclear cells in the mucosa, mucosal atrophy with hyporegeneration and enterocyte dysmaturation is observed. HIV might thus cause impairment and depletion of activated regulatory T cells in the intestinal lamina propria, which could lead not only to a breakdown of the mucosal immune barrier, resulting in a variety of opportunistic infections, but also to malabsorption, due to mucosal atrophy or enterocyte dysfunction. These findings indicate a close relationship between mucosal T cells and enterocyte proliferation and maturation.
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PMID:Cell differentiation and proliferation in the gastrointestinal tract with respect to the local immune system. 797 5

We have analyzed the V-gene usage in gamma delta T cells of the human gut and joint by using a new mAb (B18) specific for V gamma 8 of human TCR-gamma delta+ T cells. The B18+ population constituted a minor subset of the gamma delta T cells in peripheral blood (PB) of healthy persons (6 +/- 5%) and only 1 of 35 gamma delta T cell clones analyzed was positive. In contrast, the B18+ subset was a dominant gamma delta T cell population among intraepithelial lymphocytes (IEL) derived from the human intestine (74 +/- 29, p < 0.002), and two of three IEL clones from patients with coeliac disease were B18+. Interestingly, a higher proportion of B18+ gamma delta T cells was found in the synovial fluid of patients with rheumatoid arthritis (RA) (21 +/- 18%, 0.02 < p < 0.05) compared with normal PB. Furthermore, the B18+ subset was more frequent among IL-2-expanded gamma delta T cells (42 +/- 20%) derived from synovial tissue than among IL-2-expanded cells derived from synovial fluid (p < 0.002) and PB from RA patients (p < 0.02) as well as normal PB (p < 0.002). The V-gene usage of 13 gamma delta T cell clones from the synovial fluid of arthritic patients was analyzed. All B18+ clones (n = 7) expressed mRNA for V gamma 8 together with mRNA for V delta 1 (n = 5) or mRNA for V delta 3 (n = 2). None of the B18- clones expressed V gamma 8 (n = 6). We conclude that the gamma delta T cell that expresses V gamma 8, together with mainly V delta 1, is a major gamma delta T cell subset among the IEL of the gut and a highly frequent subset in the synovial tissue of patients with RA. This subset may correspond to the mouse V gamma 7+ IEL, which has a high degree of amino acid sequence homology with the human V gamma 8 protein.
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PMID:High expression of V gamma 8 is a shared feature of human gamma delta T cells in the epithelium of the gut and in the inflamed synovial tissue. 820 27

The aim of this work was to investigate the mechanism of spontaneous rat liver allograft tolerance. Liver allografts from a LEW donor into DA recipient (LEW-->DA) or of PVG-->DA were spontaneously tolerated (TOL) across a complete MHC mismatch. In contrast, DA-->LEW or PVG-->LEW liver allografts were rejected in 10 to 15 days (REJ). We examined whether donor cell migration to recipient lymphoid tissues might be associated with TOL. Many donor cells were observed in draining (celiac) lymph nodes (LN) and spleen, reaching a peak on day 1 and then decreasing rapidly thereafter. Irradiation of liver donors, which we have previously shown to delete tolerance, significantly reduced the number of donor leukocytes in recipient lymphoid tissues. While this suggested an association between donor cell migration and tolerance, the number, distribution, and type of donor cells in recipient lymphoid tissues of REJ was similar to those of TOL. Expression of cytokine mRNA in LN and spleen showed an early increase in the expression of IL-2 and IFN-gamma mRNA on day 1 and then a rapid decrease to constitutive levels. Spleen and LN levels of IL-6, IL-10, TNF-alpha, or TGF-beta mRNA showed much less up-regulation than IL-2 or IFN-gamma. Paradoxically, there was greater expression of IL-2 and IFN-gamma mRNA in TOL lymphoid tissues than in REJ, and this superinduction was partially prevented by donor irradiation. Superinduction of IL-2 and IFN-gamma was, therefore, more closely associated with TOL than was donor cell migration. This was confirmed by treatment of TOL recipients with a short course of methylprednisolone, which reduced survival of subsequent donor strain skin grafts. This finding has implications for treatment of human liver transplants and is evidence for a novel pathway of transplant tolerance.
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PMID:Tolerance to rat liver allografts. III. Donor cell migration and tolerance-associated cytokine production in peripheral lymphoid tissues. 864 43

Activated T cells, with their secretion of cytokines, probably play an important role in the pathogenesis of mucosal lesions in coeliac disease (COD) and the prominence of a T-helper (Th)1-type cytokine pattern has been reported. As the process of immunological activation in the jejunal mucosa in active CoD has been shown to also cause some differences in peripheral blood lymphocyte populations, we sought to establish any changes in the Th 1/Th2 balance in peripheral blood of patients, at different stages of CoD, relative to healthy individuals. Twenty-two CoD patients and 10 healthy controls were included in the study. The Th1/Th2 balance was examined both in resting cells and after polyclonal stimulation using two different methods: intracytoplasmic cytokine contents were measured using an intracellular staining method and three-colour flow cytometry and cytokine contents of cell culture supernatants were measured using traditional enzyme-linked immunosorbent assays (ELISAs). Interferon-gamma (IFN-gamma)-producing cells (Thl) were as prominent in untreated CoD patients and treated CoD patients as in healthy controls, while cells fitting a Th2 or ThO-type cytokine pattern were few in all groups. In ELISA assays, Th1 type (IFN-gamma or interleukin (IL)-2) cytokines were again prominent in all study groups but no statistically significant differences were found in IFN-gamma, IL-4 or IL-2 levels among the three groups. These results suggest that the increased shift towards a Th1 response is mainly restricted to the actual site of inflammation and that circulating T cells do not show a similar response, presumably because activated cells in peripheral blood are too few. Further research on cytokine profiles measuring T-cell activation in CoD should be focused on the actual tissue of inflammation.
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PMID:Normal T-helper 1/T-helper 2 balance in peripheral blood of coeliac disease patients. 1007 25

Coeliac disease (CD), an inflammatory enteropathy, is believed to be caused by immune sensitivity to ingested gluten. T-cell activation appears to be implicated in the disease although little is known regarding the role of T-cell subsets, Th1/Th2, and the cytokines they secrete. Reverse transcription-polymerase chain reaction was used to examine the mRNA expression of a wide profile of cytokines in intestinal and peripheral samples taken from active and inactive CD paediatric patients. Differential mRNA expression was observed for cytokines, between CD patients and controls, in both compartments. The percentage of samples expressing interleukin (IL)-2, interferon (IFN)-gamma, tumor necrosis factor (TNF)-beta, IL-10, IL-1beta, TNF-alpha and transforming growth factor (TGF)-beta mRNA from active CD patients was higher than from controls. A prominent finding was the expression of both Th1 (IFN-gamma, IL-2) and Th2 (IL-4, IL-10)-associated cytokine transcripts in the same biopsies and peripheral blood cells from patients with active CD implying activation of Th0 cells. The expression of IL-2 and IL-4 mRNA was not observed in peripheral blood samples from inactive CD patients associating them with disease activity. These results are important to the understanding of the inflammatory process in CD while cytokine levels may prove to be relevant markers of disease activity.
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PMID:Cytokine profile in coeliac disease. 1021 72

The immune response of PBMC to gliadin was investigated in patients with coeliac disease (CoD) by examining proliferation, MHC restriction and cytokine production. Gliadin induced low levels of proliferation in 63% of eight untreated patients, 32% of 28 treated patients and 35% of 31 healthy control subjects. In MHC restriction studies, the proliferative response to gliadin was inhibited (range 47-98% inhibition) in the presence of a MoAb to HLA-DR in each of three coeliac and three control donors studied. Using flow cytometry, increased expression of activation markers (HLA-DR and IL-2R) was demonstrated on gliadin-stimulated T cells from four of nine coeliac patients and three of seven healthy control donors. Cytokines were studied in culture supernatants using ELISA. Gliadin was a potent inducer of IL-6 and IL-10 in 100% of coeliac patients and controls, whereas IL-4 was not produced in either subject group. Gliadin induced IL-2 production in 40% of untreated patients, 42% of treated patients and 35% of healthy control donors. Interferon-gamma (IFN-gamma) in gliadin-stimulated cultures was found only in coeliac patients, observed in 33% of untreated patients and 25% of treated patients. Spontaneous secretion of both IL-2 and IFN-gamma was found more frequently in patients with untreated disease (87% of cases versus 21% of controls for IFN-gamma and 40% versus 0% for IL-2). These results suggest, as manifest by IFN-gamma production, that gliadin stimulates a Th1/Th0-like response in coeliac patients and a Th0-like response in healthy controls.
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PMID:T cell proliferation, MHC class II restriction and cytokine products of gliadin-stimulated peripheral blood mononuclear cells (PBMC). 1044 57

A 40-year-old HIV-infected woman developed nausea, vomiting, and epigastric pain and died following her third dose (per study protocol) of interleukin (IL)-2. Her HIV infection was diagnosed in 1996. Her last CD4 cell count was 390/microL, and her viral load was negligible (as of November 28, 1998). She had no known general risk factors for thrombosis other than HIV infection, injection drug abuse, and antiretroviral therapy with indinavir. Abdominal films showed no sign of mechanical obstruction but a generalized gas distention of the bowel, which was suggestive of paralytic ileus. Autopsy revealed dilation of the small bowel with extensive necrosis and hemorrhage involving all the segments. The superior and inferior mesenteric arteries revealed severe atherosclerosis. The stenotic celiac artery was occluded by a recent thrombus at the aortic ostium. Clinicians need to be aware of the potential for thrombosis and accelerated atherosclerosis in HIV-infected patients. Both injection drug abuse and protease inhibitors, such as indinavir, have been shown to be risk factors for thrombosis. However, it is likely IL-2 contributed to the severe thrombosis in this patient, although definitive proof is lacking. An acute awareness of intestinal infarction in HIV-infected patients is warranted.
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PMID:Case report. Intestinal infarction due to vascular catastrophe in an HIV-infected patient. 1118 43

T helper cell type 1 (Th1) response to gluten has been implicated in the pathogenesis of coeliac disease (CD). To characterize immunological activation and mild inflammations leading to overt CD in potential coeliac patients, jejunal biopsies were obtained from family members of patients with CD or dermatitis herpetiformis (DH). Nine family members and one latent CD, eight CD patients and eight normal controls furnished jejunal biopsy specimens. Immunohistochemical staining of sections for interleukin-1alpha (IL-1alpha), IL-2, IL-4, interferon-gamma (IFN-gamma), tumour necrosis factor alpha (TNF-alpha), CD3, gammadelta-T cell receptor (gammadelta-TCR), and alphabeta-TCR was carried out with monoclonal antibodies. Further, expression of IL-4 and IFN-gamma messenger RNA was detected by radioactive in situ hybridization in these same samples. In lamina propria, CD patients and potential CD patients had higher densities of IL-2 (P = 0.028, P = 0.043), IL-4 (P = 0.021, P = 0.034) and IFN-gamma positive cells (P = 0.000, P = 0.009) than did controls. Moreover, CD patients showed a higher density of TNF-alpha positive cells (P = 0.012, P = 0.001) than the other two groups, and expression of IFN-gamma mRNA (P = 0.035) was higher in them than in the other two study groups. Additionally, higher densities of TNF-alpha and IFN-gamma positive cells occurred in potential CD patients with high gammadelta-TCR+ intraepithelial lymphocytes (IELs). Our findings support the hypothesis that lamina propria T cells and macrophages, through their secretion of cytokines, play a central role in the pathogenesis of coeliac disease. The inflammatory cytokines found in potential CD specimens strongly suggest that these inflammatory markers can be identified long before visible villous changes have occurred.
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PMID:Inflammatory cytokines in small intestinal mucosa of patients with potential coeliac disease. 1198 96

Discovery of a number of novel and known human genes whose protein products bear striking similarity to two or more wheat gliadin domains raised the possibility that human intestinal non-HLA peptides homologous to celiac T-cell epitopes could play a role in non-HLA gene specification in celiac disease. Database searching of the entire human genome identified only 11 gut-expressed proteins with high T-cell epitope homology, particularly to the DQ2-gamma-I-gliadin epitope (i.e. TFIIA, FOXJ2 and IgD; mean BestFit quality score=40 versus random value of 24). Others were similar to DQ2-alpha-I-gliadin (i.e. PAX9; BestFit quality 46 versus 20 for random), or DQ2-alpha-II-gliadin (PHLDA1, known in mice as the T-cell death-associated gene; BestFit quality 43 versus 30 for random) epitopes. Among proteins previously screened for gliadin homology, noteworthy was achaete scute homologous protein (DQ2-alpha-I-gliadin; BestFit quality 41 versus 22 for random). With the exception of IgD, all are nuclear factors. Paying particular attention to the position of potential major histocompatibility complex (MHC) anchor residues, several were selected for testing in a DQ2-gamma-I-gliadin-restricted T-cell system. All native 10-mer peptides were inactive, even when deamidated, but V96F substitution of deamidated TFIIA amino acid residues 91-100 stimulated IL-2 release at levels exceeding the wheat gliadin positive control. Also active, but only slightly, was L1009F substitution of AIB3 amino acid residues 1004-1013. PlotSimilarity alignment of TFIIAs from eight species revealed subthreshold similarity score in the peptide region, in contrast to the highly conserved amino and carboxy termini. Molecular modeling of TFIIA[V96F] peptide points to an important juxtaposition of an upwardly projecting phenylalanine residue at peptide position 6 that likely contacts a receptor complementarity-determining region, and a downwardly projecting glutamic acid residue that fits into the shallow MHC P7 pocket. These observations tentatively point to a new multi-gene hypothesis for the initiation of celiac disease in which deamidated free human peptides with T-cell epitope homology (particularly those made more homologous by mutation) escape negative selection, as per deamidation of the HEL(48-62) peptide in the hen egg lysozyme model of autoimmunity. Deamidation following peptide release due to injury triggers inflammation, thereafter repeatedly provoked by dietary gliadin immunodominant peptides concentrated in the proximal small intestine.
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PMID:Human genome search in celiac disease: mutated gliadin T-cell-like epitope in two human proteins promotes T-cell activation. 1205 57


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