Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:6.3.4.6 (urease)
7,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Helicobacter pylori has been identified as a dominant factor in the pathogenesis of duodenal ulcer. The aim of this study was to examine peripheral blood and gastric lymphocyte proliferation and cytokine production in patients with H pylori colonisation. Sixty five dyspeptic patients attending for endoscopy were studied; 35 of these were H pylori positive and 30 H pylori negative as assessed by culture, histology, and rapid urease test. H pylori antigen was capable of stimulating peripheral blood lymphocyte proliferative responses even in H pylori negative patients. Peripheral blood lymphocyte proliferative responses to H pylori (but not to purified protein derivative or phythaemagglutinin) were significantly lower in H pylori positive than H pylori negative patients. Similarly, antigen specific proliferative responses and interferon gamma production by gastric lamina propria lymphocytes were also depressed in H pylori positive patients compared with H pylori negative patients. CD8 and CD22 positive lamina propria lymphocytes were increased in H pylori positive patients. These data show that antigen specific responses to H pylori are significantly lower in H pylori positive patients and could indicate activation of antigen specific suppression.
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PMID:Gastric T lymphocyte responses to Helicobacter pylori in patients with H pylori colonisation. 795 91

Studies regarding the nature of cell-mediated immunity in Helicobacter pylori infection and its role in pathogenesis have yielded controversial results. To address this issue in a controlled manner, we have employed the well-characterized Helicobacter felis-mouse model. Immunized/challenged and nonimmunized/infected mice were evaluated for cellular proliferation, gastric inflammation, and cytokine and Ab production at various times after infection. We observed two types of cell-mediated immune responses depending on the nature of the Ag preparation. The first response is a Helicobacter-independent response, present in all experimental groups, which is directed toward Ags such as urease and heat shock proteins. The second is a Helicobacter-dependent cellular response restricted to mice previously exposed to Helicobacter Ags either by immunization or infection. This response was not seen in noninfected controls. The Helicobacter-dependent cellular response had a Th1 phenotype, as either infected or immunized/challenged mice demonstrated local and systemic production of IFN-gamma and undetectable levels of IL-4 or IL-5. Cellular proliferation correlated with the severity of gastric inflammation in both immunized/challenged (protected) and nonimmunized/infected mice. Finally, in vivo neutralization of IFN-gamma resulted in a significant reduction of gastric inflammation in H. felis-infected, as well as immunized/challenged, mice. This treatment also revealed the presence of Th2 cells, restricted to immunized/challenged mice, as demonstrated by local and systemic production of IL-4 in these mice. These data demonstrate that Helicobacter infection and/or immunization stimulate a predominantly Th1-type, Ag-specific response and promote a local delayed-type hypersensitivity response in the stomach that may be inhibited by depletion of IFN-gamma.
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PMID:Helicobacter-specific cell-mediated immune responses display a predominant Th1 phenotype and promote a delayed-type hypersensitivity response in the stomachs of mice. 864 19

Chronic antral gastritis following Helicobacter pylori (Hp) infection is characterized by a cellular inflammatory infiltrate whose cytokines may represent a host-dependent factor influencing the outcome of the infection. The pattern of cytokines produced by the immunologically active cells in the gastric antrum was analyzed at the mRNA level in antral biopsies from five Hp-infected patients with duodenal ulcer and three Hp-negative dyspeptic controls. T cell clones were generated from parallel antral biopsies of the same Hp-infected patients and assessed for reactivity to Hp Ags, cytokine profile, and effector functions. Antral biopsies from all Hp-infected patients showed IFN-gamma, TNF-alpha, and IL-12, but not IL-4, mRNA expression, whereas no cytokine mRNA signal was found in the mucosa of controls. A total of 24 out of the 163 CD4+ T cell clones (15%) derived from Hp-infected patients proliferated in response to a Hp lysate; 11 clones (46%) also reacted with Cag-A, 2 with Vac-A, and 1 with urease. Upon Ag stimulation, 20 out of the 24 Hp-reactive clones (83%) produced IFN-gamma, but not IL-4 or IL-5 (Th1-like), whereas 4 produced IFN-gamma, IL-4, and IL-5 (Th0-like). All Hp-specific clones secreted high levels of TNF-alpha. At low T:B cell ratio, Hp-specific clones expressed Ag-dependent helper function for B cell proliferation and Ig production, whereas at higher T:B cell ratios, 15 Th1 and 2 Th0 clones lysed Ag-pulsed autologous EBV-transformed B cells. Results provide evidence for Hp-specific Th1 effectors in the gastric antrum of Hp-infected patients, where they may play a role in the genesis of either peptic ulcer or Hp-associated gastric B cell lymphoma.
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PMID:T helper 1 effector cells specific for Helicobacter pylori in the gastric antrum of patients with peptic ulcer disease. 899 17

The urocanic acid cis isomer (cis-UCA) is a possible cutaneous photoreceptor for the immunomodulatory phenomena that follow ultraviolet B irradiation. Several experiments in animals show an inhibitory action of cis-UCA on cellular immunity. However, the action of cis-UCA on the synthesis of cytokines in keratinocytes remains unknown. Long-term cultures of normal human keratiocytes were prepared in a serum-free medium, and stimulated with 1 microgram/ml of phorbol 12-myristate 13-acetate (TPA) and UCA or UVB-UCA (10-100 micrograms/ml). Synthesis of the following cytokines was measured using ELISA and Northern blot techniques: TNF-alpha, IL-1 alpha, IL-1 beta, IL-6, IL-8 and TGF-beta 1. TPA increased TNF-alpha protein levels in culture supernatants. No changes in Il-1 alpha and IL-1 beta protein levels were detected in basal culture supernatant after TPA stimulus. TPA augmented RNA expression for TNF-alpha, IL-1 alpha, IL-1 beta and TGF-beta 1. UCA isomers did not induce cytokine changes in protein synthesis. Expression of IL-1 alpha and IL-1 beta genes was increased after exposure to 100 micrograms/ml UVB-UCA (70 micrograms/ml cis-UCA). A slight increase in TNF-alpha RNA expression was detected when the dose of UVB-UCA reached 100 micrograms/ml. No effects on cytokine synthesis were found after UCA stimulus. These results suggest that low doses of cis-UCA do not effect cytokine synthesis by keratinocytes.
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PMID:Effects of low concentrations of cis- and trans-urocanic acid on cytokine elaboration by keratinocytes. 918 8

Helicobacter pylori (Hp) infection almost invariably results in chronic antral gastritis, but only a proportion of patients develop peptic ulcer. Some Hp strains may be more ulcerogenic than others, but some ulcerogenic mechanisms may also depend on the type of the host immune response. In this study, the antigen specificity and the cytokine profile of 53 Hp-specific CD4+ T cell clones derived from the antral mucosa of five patients with Hp-induced uncomplicated chronic gastritis (CG) were assessed and compared with those of 34 Hp-specific CD4+ T cell clones derived from six Hp-infected patients with chronic gastritis and peptic ulcer (CG-PU). The majority (28/34; 82%) of gastric Hp-specific T cell clones from CG-PU patients expressed the Th1 profile and 17 (all Th1) of the 34 clones were specific for cytotoxin-associated protein (CagA). In contrast, 34 (64%) of the 53 Hp-specific gastric T cell clones derived from CG patients were able to secrete both Th1 and Th2 cytokines (Th0 profile) and only 36% expressed a polarized Th1 profile. The majority (85%) of Hp-specific clones from CG patients recognized Hp antigens other than CagA, since 13/53 (25%) were specific for urease, 6 (11%) for VacA, 6 (11%) for HSP and 20 (38%) for other undefined Hp antigens. Results provide evidence that the type of T helper cell response against Hp may vary according to the antigen involved and suggest that a polarized Th1 response may play a role in the genesis of peptic ulcer, whereas a local Th0 response, including interleukin-4 production, may represent an individual host factor which contributes to lower the degree of gastric inflammation and prevent ulcer complication.
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PMID:Different cytokine profile and antigen-specificity repertoire in Helicobacter pylori-specific T cell clones from the antrum of chronic gastritis patients with or without peptic ulcer. 924 87

Live Salmonella typhimurium phoPc bacteria were tested as mucosal vaccine vectors to deliver Helicobacter pylori antigens. The genes encoding the A and B subunits of H. pylori urease were introduced into S. typhimurium phoPc and expressed under the control of a constitutive tac promoter (tac-ureAB) or a two-phase T7 expression system (cT7-ureAB). Both recombinant Salmonella strains expressed the two urease subunits in vitro and were used to nasally immunize BALB/c mice. The plasmid carrying cT7-ureAB was stably inherited by bacteria growing or persisting in the spleen, lungs, mesenteric or cervical lymph nodes, and Peyer's patches of immunized mice, while the plasmid carrying tac-ureAB was rapidly lost. Spleen and Peyer's patch CD4+ lymphocytes from mice immunized with S. typhimurium phopc cT7-ureAB proliferated in vitro in response to urease, whereas cells from mice given S. typhimurium phoPc alone did not. Splenic CD4+ cells from mice immunized with phoPc cT7-ureAB secreted gamma interferon and interleukin 10, while Peyer's patch CD4+ cells did not secrete either cytokine. Specific H. pylori anti-urease immunoglobulin G1 (IgG1) and IgG2A antibodies were detected following immunization, confirming that both Th1- and Th2-type immune responses were generated by the live vaccine. Sixty percent of the mice (9 of 15) immunized with S. typhimurium phoPc cT7-ureAB were found to be resistant to infection by H. pylori, while all mice immunized with phoPc tac-ureAB (15 of 15) or phoPc (15 of 15) were infected. Our data demonstrate that H. pylori urease delivered nasally by using a vaccine strain of S. typhimurium can trigger Th1- and Th2-type responses and induce protective immunity against Helicobacter infection.
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PMID:Mice are protected from Helicobacter pylori infection by nasal immunization with attenuated Salmonella typhimurium phoPc expressing urease A and B subunits. 945 12

Cytokines have been proposed to play an important role in Helicobacter pylori-associated gastroduodenal diseases, but the exact mechanism of the cytokine induction remains unclear. H. pylori urease, a major component of the soluble proteins extracted from bacterial cells, is considered to be one of the virulence factors for the inflammation in the gastric mucosa that is produced in H. pylori infection. However, the response of human gastric epithelial cells to the stimulation of urease has not been investigated. In the present study, we used human gastric epithelial cells in a primary culture system and examined whether H. pylori urease stimulates the gastric epithelial cells to induce proinflammatory cytokines by reverse transcription-PCR and enzyme-linked immunosorbent assay. First, by using peripheral blood mononuclear cells (PBMC) and a gastric cancer cell line (MKN-45 cells), we confirmed the ability of purified H. pylori urease to induce the production of proinflammatory cytokines. Furthermore, we demonstrated that the human gastric epithelial cells produced interleukin-6 (IL-6) and tumor necrosis factor alpha, but not IL-8, following stimulation with purified urease. The patterns of cytokine induction differed among human PBMC, MKN-45 cells, and human gastric epithelial cells. These results suggest that the human gastric epithelial cells contribute to the induction of proinflammatory cytokines by the stimulation of H. pylori urease, indicating that the epithelial cells were involved in the mucosal inflammation that accompanied H. pylori infection.
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PMID:Cytokine expression and production by purified Helicobacter pylori urease in human gastric epithelial cells. 1063 31

The relationship of Helicobacter felis, a bacterium observed in the stomachs of cats, to gastric disease is unclear. The objective of this study was to determine if H. felis infection alters gastric histopathology, proinflammatory cytokine expression, and secretory function and evokes a humoral immune response in cats. Five specific-pathogen-free (SPF) Helicobacter-free cats were studied before and for 1 year after oral inoculation with H. felis (ATCC 49179). Four SPF H. felis-uninfected cats served as controls. The stomachs of all five H. felis-inoculated cats became colonized, as determined by urease activity, histopathology, PCR, culture, and transmission electron microscopy of serial gastric biopsies at 0, 3, 5, 8, and 12 months. Uninoculated cats remained Helicobacter free. Lymphoid follicular hyperplasia, atrophy, and fibrosis were observed primarily in the pylorus of infected cats. Mild mononuclear inflammation was detected in both infected and uninfected cats, but was more extensive in infected cats, with pangastric inflammation, eosinophilic infiltrates, and cardia gastritis observed only in infected cats. No upregulation of antral mucosal interleukin 1alpha (IL-1alpha), IL-1beta, or tumor necrosis factor alpha was detected by reverse transcription-PCR in any cat. The gastric secretory axes, assessed by fasting plasma gastrin, antral mucosal gastrin and somatostatin immunoreactivity, and pentagastrin-stimulated gastric acid secretion, were similar in both infected and uninfected cats. Gradual seroconversion (immunoglobulin G) was observed in four of five infected cats, with enzyme-linked immunosorbent assay values reaching 4x to 12x baseline 12 months postinfection. These findings indicate that H. felis infection in cats induces lymphoid follicular hyperplasia, mild gastritis, and seroconversion, but is associated with normal gastric secretory function.
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PMID:Helicobacter felis infection is associated with lymphoid follicular hyperplasia and mild gastritis but normal gastric secretory function in cats. 1063 46

To elucidate the pathogenesis of Helicobacter pylori-associated gastritis, we studied immune responses of C57BL/6J wild-type (WT), SCID, and gene deficient (IFN-gamma-/- and IL-4-/-) mice following infection with a pathogenic isolate of H. pylori (SPM326). During early infection in WT mice, mononuclear and polymorphonuclear cells accumulated in the gastric lamina propria, and the numbers of cells in the inflamed mucosa expressing IFN-gamma, but not IL-4, mRNA rose significantly (p < 0.005), consistent with a local Th1 response. Splenic T cells from the same infected WT mice produced high levels of IFN-gamma, no detectable IL-4, and low amounts of IL-10 following in vitro H. pylori urease stimulation, reflecting a systemic Th1 response. Infected C57BL/6J SCID mice did not develop gastric inflammation despite colonization by many bacteria. Infected C57BL/10J and BALB/c mice also did not develop gastric inflammation and displayed a mixed Th1/Th2 splenic cytokine profile. These data imply a major role for the Th1 cytokine IFN-gamma in H. pylori-associated gastric inflammation in C57BL/6J mice. Compared with WT animals, infected IL-4-/- animals had more severe gastritis and higher levels of IFN-gamma production by urease-stimulated splenocytes (p < 0.01), whereas IFN-gamma-/- mice exhibited no gastric inflammation and higher levels of IL-4 production by stimulated splenocytes. These findings establish C57BL/6J mice as an important model for H. pylori infection and demonstrate that up-regulated production of IFN-gamma, in the absence of the opposing effects of IL-4 (and possibly IL-10), plays a pivotal role in promoting H. pylori-induced mucosal inflammation.
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PMID:Helicobacter pylori-induced mucosal inflammation is Th1 mediated and exacerbated in IL-4, but not IFN-gamma, gene-deficient mice. 1087 79

The gastric inflammatory and immune response in Helicobacter pylori infection may be due to the effect of different H. pylori products on innate immune mechanisms. The aim of this study was to determine whether bacterial components could modulate cytokine production in vitro and thus contribute to Th1 polarization of the gastric immune response observed in vivo. The effect of H. pylori recombinant urease, bacterial lysate, intact bacteria, and bacterial DNA on proliferation and cytokine production by peripheral blood mononuclear cells (PBMCs) from H. pylori-negative donors was examined as a model for innate cytokine responses. Each of the different H. pylori preparations induced gamma interferon (IFN-gamma) and interleukin-12p40 (IL-12p40), but not IL-2 or IL-5, production, and all but H. pylori DNA stimulated release of IL-10. Addition of anti-IL-12 antibody to cultures partially inhibited IFN-gamma production. In addition, each bacterial product inhibited mitogen-stimulated IL-2 production by PBMCs and Jurkat T cells. The inhibitory effect of bacterial products on IL-2 production correlated with inhibition of mitogen-stimulated lymphocyte proliferation, although urease inhibited IL-2 production without inhibiting proliferation, suggesting that inhibition of IL-2 production alone is not sufficient to inhibit lymphocyte proliferation. The results of these studies demonstrate that Th1 polarization of the gastric immune response may be due in part to the direct effects of multiple different H. pylori components that enhance IFN-gamma and IL-12 production while inhibiting both IL-2 production and cell proliferation that may be necessary for Th2 responses.
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PMID:Modulation of innate cytokine responses by products of Helicobacter pylori. 1103 34


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