WorldWideScience

Sample records for pylori induces mir-155

  1. Helicobacter pylori induces miR-155 in T cells in a cAMP-Foxp3-dependent manner.

    Directory of Open Access Journals (Sweden)

    Lina Fassi Fehri

    Full Text Available Amongst the most severe clinical outcomes of life-long infections with Helicobacter pylori is the development of peptic ulcers and gastric adenocarcinoma--diseases often associated with an increase of regulatory T cells. Understanding H. pylori-driven regulation of T cells is therefore of crucial clinical importance. Several studies have defined mammalian microRNAs as key regulators of the immune system and of carcinogenic processes. Hence, we aimed here to identify H. pylori-regulated miRNAs, mainly in human T cells. MicroRNA profiling of non-infected and infected human T cells revealed H. pylori infection triggers miR-155 expression in vitro and in vivo. By using single and double H. pylori mutants and the corresponding purified enzymes, the bacterial vacuolating toxin A (VacA and gamma-glutamyl transpeptidase (GGT plus lipopolysaccharide (LPS tested positive for their ability to regulate miR-155 and Foxp3 expression in human lymphocytes; the latter being considered as the master regulator and marker of regulatory T cells. RNAi-mediated knockdown (KD of the Foxp3 transcription factor in T cells abolished miR-155 expression. Using adenylate cyclase inhibitors, the miR-155 induction cascade was shown to be dependent on the second messenger cyclic adenosine monophosphate (cAMP. Furthermore, we found that miR-155 directly targets the protein kinase A inhibitor alpha (PKIalpha mRNA in its 3'UTR, indicative of a positive feedback mechanism on the cAMP pathway. Taken together, our study describes, in the context of an H. pylori infection, a direct link between Foxp3 and miR-155 in human T cells and highlights the significance of cAMP in this miR-155 induction cascade.

  2. Inhibition of miR-155 Protects Against LPS-induced Cardiac Dysfunction and Apoptosis in Mice

    Directory of Open Access Journals (Sweden)

    Hui Wang

    2016-01-01

    Full Text Available Sepsis-induced myocardial dysfunction represents a major cause of death in intensive care units. Dysregulated microRNAs (miR-155 has been implicated in multiple cardiovascular diseases and miR-155 can be induced by lipopolysaccharide (LPS. However, the role of miR-155 in LPS-induced cardiac dysfunction is unclear. Septic cardiac dysfunction in mice was induced by intraperitoneal injection of LPS (5 mg/kg and miR-155 was found to be significantly increased in heart challenged with LPS. Pharmacological inhibition of miR-155 using antagomiR improved cardiac function and suppressed cardiac apoptosis induced by LPS in mice as determined by echocardiography, terminal deoxynucleotidyl transferase nick-end labeling (TUNEL assay, and Western blot for Bax and Bcl-2, while overexpression of miR-155 using agomiR had inverse effects. Pea15a was identified as a target gene of miR-155, mediating its effects in controlling apoptosis of cardiomyocytes as evidenced by luciferase reporter assays, quantitative real time-polymerase chain reaction, Western blot, and TUNEL staining. Noteworthy, miR-155 was also found to be upregulated in the plasma of patients with septic cardiac dysfunction compared to sepsis patients without cardiac dysfunction, indicating a potential clinical relevance of miR-155. The receiver-operator characteristic curve indicated that plasma miR-155 might be a biomarker for sepsis patients developing cardiac dysfunction. Therefore, inhibition of miR-155 represents a novel therapy for septic myocardial dysfunction.

  3. Targeting miR-155 suppresses proliferation and induces apoptosis of HL-60 cells by targeting Slug/PUMA signal.

    Science.gov (United States)

    Liang, Hui; Dong, Ziyan; Liu, Jiang-Feng; Chuang, Wei; Gao, Li-Zhen; Ren, Yu-Guo

    2016-10-27

    Recent studies have shown that high miR-155 expression was associated with poor prognosis in patients with acute myelogeneous leukemia (AML). Furthermore, targeting miR-155 results in monocytic differentiation and apoptosis. However, the exact role and mechanisms of miR-155 in human AML remains speculative. HL-60 cells were treated with anti-miR-155 for 72 h. Cell growth and apoptosis in vitro were detected by MTT, BrdU proliferation, colony formation and flow cytometry assay. The effect of anti-miR-155 on growth of HL-60 cells was also evaluated in a leukemia mouse model. Slug cDNA and PUMA siRNA trannsfection was used to assess the signal pathway. Different protein expression was detected by western blot assay and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assay. The results shown that targeting miR-155 resulted in a 24-fold decrease of miR-155 expression compared to negative control in the HL-60 cells. Targeting miR-155 significantly downregulated Slug and upregulated PUMA expression, and decreased HL-60 cell growth by 70% , impaired colony formation by approximately 60%, and increased HL-60 cell apoptosis by 45%. Targeting PUMA reversed miR-155 sliencing-induced proliferation and apoptosis of HL-60 cells. Restoration of Slug decreased PUMA expression. In murine engraftment models of HL-60 cells, we showed that targeting miR-155 was able to reduce tumor growth. This was accompanied with decreased Slug expression and increased PUMA expression in these tumors. Collectively, our findings strongly suggest targeting miR-155 exhibited in vivo and in vitro antileukemic activities in AML through a novel mechanism resulting in inhibition of Slug expression and increase of PUMA expression.

  4. Inhibition of IFN-γ-Induced Nitric Oxide Dependent Antimycobacterial Activity by miR-155 and C/EBPβ

    Directory of Open Access Journals (Sweden)

    Yongwei Qin

    2016-04-01

    Full Text Available miR-155 (microRNA-155 is an important non-coding RNA in regulating host crucial biological regulators. However, its regulatory function in mycobacterium infection remains unclear. Our study demonstrates that miR-155 expression is significantly increased in macrophages after Mycobacterium marinum (M.m infection. Transfection with anti-miR-155 enhances nitric oxide (NO synthesis and decreases the mycobacterium burden, and vice versa, in interferon γ (IFN-γ activated macrophages. More importantly, miR-155 can directly bind to the 3′UTR of CCAAT/enhancer binding protein β (C/EBPβ, a positive transcriptional regulator of nitric oxide synthase (NOS2, and regulate C/EBPβ expression negatively. Knockdown of C/EBPβ inhibit the production of nitric oxide synthase and promoted mycobacterium survival. Collectively, these data suggest that M.m-induced upregulation of miR-155 downregulated the expression of C/EBPβ, thus decreasing the production of NO and promoting mycobacterium survival, which may provide an insight into the function of miRNA in subverting the host innate immune response by using mycobacterium for its own profit. Understanding how miRNAs partly regulate microbicidal mechanisms may represent an attractive way to control tuberculosis infectious.

  5. Interleukin-10 inhibits lipopolysaccharide induced miR-155 precursor stability and maturation.

    Directory of Open Access Journals (Sweden)

    Sylvia T Cheung

    Full Text Available The anti-inflammatory cytokine interleukin-10 (IL-10 is essential for attenuating the inflammatory response, which includes reducing the expression of pro-inflammatory microRNA-155 (miR-155 in lipopolysaccharide (LPS activated macrophages. miR-155 enhances the expression of pro-inflammatory cytokines such as TNFα and suppresses expression of anti-inflammatory molecules such as SOCS1. Therefore, we examined the mechanism by which IL-10 inhibits miR-155. We found that IL-10 treatment did not affect the transcription of the miR-155 host gene nor the nuclear export of pre-miR-155, but rather destabilized both pri-miR-155 and pre-miR-155 transcripts, as well as interfered with the final maturation of miR-155. This inhibitory effect of IL-10 on miR-155 expression involved the contribution of both the STAT3 transcription factor and the phosphoinositol phosphatase SHIP1. This is the first report showing evidence that IL-10 regulates miRNA expression post-transcriptionally.

  6. Selective inhibition of IFNG-induced autophagy by Mir155- and Mir31-responsive WNT5A and SHH signaling.

    Science.gov (United States)

    Holla, Sahana; Kurowska-Stolarska, Mariola; Bayry, Jagadeesh; Balaji, Kithiganahalli Narayanaswamy

    2014-02-01

    Autophagy is one of the major immune mechanisms engaged to clear intracellular infectious agents. However, several pathogens have evolved strategies to evade autophagy. Here, we demonstrated that Mycobacteria, Shigella, and Listeria but not Klebsiella, Staphylococcus, and Escherichia inhibit IFNG-induced autophagy in macrophages by evoking selective and robust activation of WNT and SHH pathways via MTOR. Utilization of gain- or loss-of-function analyses as well as mir155-null macrophages emphasized the role of MTOR-responsive epigenetic modifications in the induction of Mir155 and Mir31. Importantly, cellular levels of PP2A, a phosphatase, were regulated by Mir155 and Mir31 to fine-tune autophagy. Diminished expression of PP2A led to inhibition of GSK3B, thus facilitating the prolonged activation of WNT and SHH signaling pathways. Sustained WNT and SHH signaling effectuated the expression of anti-inflammatory lipoxygenases, which in tandem inhibited IFNG-induced JAK-STAT signaling and contributed to evasion of autophagy. Altogether, these results established a role for new host factors and inhibitory mechanisms employed by the pathogens to limit autophagy, which could be targeted for therapeutic interventions.

  7. Repression of human activation induced cytidine deaminase by miR-93 and miR-155

    Directory of Open Access Journals (Sweden)

    Holton Nathaniel W

    2011-08-01

    Full Text Available Abstract Background Activation Induced cytidine Deaminase (AID targets the immunoglobulin genes of activated B cells, where it converts cytidine to uracil to induce mutagenesis and recombination. While essential for immunoglobulin gene diversification, AID misregulation can result in genomic instability and oncogenic transformation. This is classically illustrated in Burkitt's lymphoma, which is characterized by AID-induced mutation and reciprocal translocation of the c-MYC oncogene with the IgH loci. Originally thought to be B cell-specific, AID now appears to be misexpressed in several epithelial cancers, raising the specter that AID may also participate in non-B cell carcinogenesis. Methods The mutagenic potential of AID argues for the existence of cellular regulators capable of repressing inappropriate AID expression. MicroRNAs (miRs have this capacity, and we have examined the publically available human AID EST dataset for miR complementarities to the human AID 3'UTR. In this work, we have evaluated the capacity of two candidate miRs to repress human AID expression in MCF-7 breast carcinoma cells. Results We have discovered moderate miR-155 and pronounced miR-93 complementary target sites encoded within the human AID mRNA. Luciferase reporter assays indicate that both miR-93 and miR-155 can interact with the 3'UTR of AID to block expression. In addition, over-expression of either miR in MCF-7 cells reduces endogenous AID protein, but not mRNA, levels. Similarly indicative of AID translational regulation, depletion of either miR in MCF-7 cells increases AID protein levels without concurrent increases in AID mRNA. Conclusions Together, our findings demonstrate that miR-93 and miR-155 constitutively suppress AID translation in MCF-7 cells, suggesting widespread roles for these miRs in preventing genome cytidine deaminations, mutagenesis, and oncogenic transformation. In addition, our characterization of an obscured miR-93 target site located

  8. Hedyotis diffusa plus Scutellaria barbata Induce Bladder Cancer Cell Apoptosis by Inhibiting Akt Signaling Pathway through Downregulating miR-155 Expression

    Directory of Open Access Journals (Sweden)

    Li-Tao Pan

    2016-01-01

    Full Text Available Traditional Chinese medicine is increasingly used to treat cancer. Our clinical experiences identify Hedyotis diffusa plus Scutellaria barbata as the most common herb-pair (couplet medicinal used for the core treatment of bladder cancer. This study aims to investigate the antitumor effect of the herb-pair in bladder cancer cells. The results show that Hedyotis diffusa plus Scutellaria barbata inhibited bladder cancer cell growth and clone formation in a dose-dependent and time-dependent manner. It also induced cell apoptosis through decreasing Akt activation and reducing the expression of antiapoptotic proteins Bcl-2 and Mcl-1. Further experiments showed that miR-155 was reduced by the herb-pair and miRNA-155 inhibitor induced cell apoptosis and suppressed Akt activation. Overexpression of miR-155 reversed herb-pair induced cell apoptosis through activating Akt pathway in both bladder cancer cell lines. The findings reveal that Hedyotis diffusa plus Scutellaria barbata reduce Akt activation through reducing miR-155 expression, resulting in cell apoptosis. It demonstrated the potential mechanism of Hedyotis diffusa plus Scutellaria barbata for the core treatment of bladder cancer.

  9. Targeting miR-155 to Treat Experimental Scleroderma.

    Science.gov (United States)

    Yan, Qingran; Chen, Jie; Li, Wei; Bao, Chunde; Fu, Qiong

    2016-02-01

    Scleroderma is a refractory autoimmune skin fibrotic disorder. Alterations of microRNAs in lesional skin could be a new approach to treating the disease. Here, we found that expression of miR-155 was up regulated in lesional skin tissue from patients with either systemic or localized scleroderma, and correlated with fibrosis area. Then we demonstrated the potential of miR-155 as a therapeutic target in pre-clinical scleroderma models. MiR-155(-/-) mice were resistant to bleomycin induced skin fibrosis. Moreover, topical antagomiR-155 could effectively treat mice primed with subcutaneous bleomycin. In primary skin fibroblast, miR-155 silencing could inhibit collagen synthesis function, as well as signaling intensity of two pro-fibrotic pathways, Wnt/β-catenin and Akt, simultaneously. We further showed that miR-155 could regulate the two pathways via directly targeting casein kinase 1α (CK1α) and Src homology 2-containing inositol phosphatase-1 (SHIP-1), as previous reports. Mice with miR-155 knockout or topical antagomir-155 treatment showed inhibited Wnt/β-catenin and Akt signaling in skin upon bleomycin challenge. Together, our data suggest the potential of miR-155 silencing as a promising treatment for dermal fibrosis, especially in topical applications.

  10. Expression level of miR-155 in peripheral blood

    Institute of Scientific and Technical Information of China (English)

    Yu-Hui Zhang; Liang-Hua Xia; Jia-Mei Jin; Ming Zong; Ming Chen; Bo Zhang

    2015-01-01

    Objective:To investigate the relationship between the expression level of miR-155 and the severity of coronary lesion, and explore the action mechanism.Methods: Peripheral blood mononuclear cells (PBMC) were isolated form blood simple from patients with acute myocardial infarction (AMI), unstable angina (UAP), stable angina (SAP) and chest pain syndrome (CPS). RT-PCR was performed to analysis the expression level of miR-155 in peripheral blood mononuclear cells, plasma and RAW264.7 macrophagocyte. MTT was used to analyze the cell viability of OxLDL treated RAW264.7 macrophagocyte.Results: The expression level of miR-155 in blood sample from coronary heart disease patients was much lower than in the blood sample of non-coronary heart disease (P<0.05). The level of miR-155 in PBMCs was much higher in the blood sample from CPS group than the other three group, and the level of miR-155 in plasma was higher in the CPS group than in the UAP and the AMI group, the difference was statistically significant (P<0.05). The expression level of miR-155 in PBMCs is positively associated with the level in the plasma (r=0.861,P=0.000). OxLDL can induce the expression of miR-155 in RAW264.7 macrophagocyte, decrease the cell viability of RAW264.7 macrophagocyte, and with the concentration and the treatment time of OxLDL increased, the effort become more obvious. The inhibition effort of OxLDL to RAW264.7 macrophagocyte with high miR-155 expression is much lower than the control group, and it is statistically significant after treated for 12, 24 and 48 h.Conclusions: miR-155 plays a protective role in the progression of atherosclerosis, and it may be achieved by reducing the apoptosis effort of OxLDL to RAW264.7 macrophagocyte.

  11. TLR9-induced miR-155 and Ets-1 decrease expression of CD1d on B cells in SLE.

    Science.gov (United States)

    Liu, Fei; Fan, Hongye; Ren, Deshan; Dong, Guanjun; Hu, Erling; Ji, Jianjian; Hou, Yayi

    2015-07-01

    B cells present lipid antigens to CD1d-restricted invariant natural killer T (iNKT) cells to maintain autoimmune tolerance, and this process is disrupted in systemic lupus erythematosus (SLE). Inflammation may inhibit CD1d expression to exacerbate the pathology of lupus. However, how inflammation regulates CD1d expression on B cells is unclear in SLE. In the present study, we showed that the surface expression of CD1d on B cells from SLE mice was decreased and that stimulation of inflammatory responses through TLR9 decreased the membrane and total CD1d levels of CD1d on B cells. Moreover, inflammation-related microRNA-155 (miR-155) negatively correlated with the expression of CD1d in B cells. miR-155 directly targeted the 3'-untranslated region (3'-UTR) of CD1d upon TLR9 activation in both humans and mice. The inhibitory effects of miR-155 on CD1d expression in B cells impaired their antigen-presenting capacity to iNKT cells. In addition, Ets-1, a susceptibility gene of SLE, also directly regulated the expression of the CD1d gene at the transcriptional level. These findings provide new insight into the mechanism underlying decreased CD1d expression on B cells in SLE, suggesting that inhibition of inflammation may increase CD1d expression in B cells to ameliorate SLE via modulating iNKT cells.

  12. Helminth Excreted/Secreted Antigens Repress Expression of LPS-Induced Let-7i but Not miR-146a and miR-155 in Human Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Luis I. Terrazas

    2013-01-01

    Full Text Available MicroRNAs have emerged as key regulators of immune responses. They influence immune cells' function and probably the outcome of several infections. Currently, it is largely unknown if helminth parasites and their antigens modify host microRNAs expression. The aim of this study was to explore if excreted/secreted antigens of Taenia crassiceps regulate LPS-induced miRNAs expression in human Dendritic Cells. We found that these antigens repressed LPS-let-7i induction but not mir-146a or mir-155 and this correlates with a diminished inflammatory response. This let-7i downregulation in Dendritic Cells constitutes a novel feature of the modulatory activity that helminth-derived antigens exert on their host.

  13. MiR-155 induction by microbes/microbial ligands requires NF-kB-dependent de novo protein synthesis

    Directory of Open Access Journals (Sweden)

    Susheela eTridandapani

    2012-06-01

    Full Text Available MiR-155 regulates numerous aspects of innate and adaptive immune function. This miR is induced in response to toll-like receptor ligands, cytokines, and microbial infection. We have previously shown that miR-155 is induced in monocytes/macrophages infected with Francisella tularensis and suppresses expression of the inositol phosphatase SHIP to enhance activation of the PI3K/Akt pathway, which in turn promotes favorable responses for the host. Here we examined how miR-155 expression is regulated during infection. First, our data demonstrate that miR-155 can be induced through soluble factors of bacterial origin and not the host. Second, miR-155 induction is not a direct effect of infection and it requires NF-κB signaling to up-regulate fos/jun transcription factors. Finally, we demonstrate that the requirement for NF-κB-dependent de novo protein synthesis is globally shared by microbial ligands and live bacteria. This study provides new insight into the complex regulation of miR-155 during microbial infection.

  14. Deregulation of dicer and mir-155 expression in liposarcoma

    Science.gov (United States)

    Vincenzi, Bruno; Iuliani, Michele; Zoccoli, Alice; Pantano, Francesco; Fioramonti, Marco; De Lisi, Delia; Frezza, Anna Maria; Rabitti, Carla; Perrone, Giuseppe; Muda, Andrea Onetti; Russo, Antonio; Giordano, Antonio; Santini, Daniele; Dei Tos, Angelo Paolo; Tonini, Giuseppe

    2015-01-01

    Liposarcoma (LPS) is the most common soft tissue sarcoma. It has been demonstrated that mir-155 was the most overexpressed miRNA in well-differentiated LPS(WDLPS)/dedifferentiated LPS (DDLPS). The aim of this study is to evaluate the involvement of Dicer, Drosha and mir-155 in development of LPS and their possible role in stratification of different histological subtypes. Dicer, Drosha and mir-155 mRNA levels were analyzed in formalin-fixed paraffin-embedded specimens from patients diagnosed with 62 LPS and compared with samples of adipose tissues of healthy donors. The experimental data were obtained using qRT-PCR comparing Dicer, Drosha and mir-155 expression levels in tumor samples versus normal fat. The tumor samples from LPS patients showed a significantly lower Dicer expression versus normal adipose tissue, while Drosha levels did not differ. Concerning mir155 expression levels, our results demonstrated a significant mir-155 up-regulation in all LPS subtypes versus normal adipose tissue except for WDLS. These findings demonstrate for the first time that Dicer is deregulated in LPS and show that mir-155 is differentially expressed in LPS subgroups and it could be a promising tool to improve LPS disease stratification and differential diagnosis. PMID:25888631

  15. MiR-155 induction by F. novicida but not the virulent F. tularensis results in SHIP down-regulation and enhanced pro-inflammatory cytokine response.

    Directory of Open Access Journals (Sweden)

    Thomas J Cremer

    Full Text Available The intracellular gram-negative bacterium Francisella tularensis causes the disease tularemia and is known for its ability to subvert host immune responses. Previous work from our laboratory identified the PI3K/Akt pathway and SHIP as critical modulators of host resistance to Francisella. Here, we show that SHIP expression is strongly down-regulated in monocytes and macrophages following infection with F. tularensis novicida (F.n.. To account for this negative regulation we explored the possibility that microRNAs (miRs that target SHIP may be induced during infection. There is one miR that is predicted to target SHIP, miR-155. We tested for induction and found that F.n. induced miR-155 both in primary monocytes/macrophages and in vivo. Using luciferase reporter assays we confirmed that miR-155 led to down-regulation of SHIP, showing that it specifically targets the SHIP 3'UTR. Further experiments showed that miR-155 and BIC, the gene that encodes miR-155, were induced as early as four hours post-infection in primary human monocytes. This expression was dependent on TLR2/MyD88 and did not require inflammasome activation. Importantly, miR-155 positively regulated pro-inflammatory cytokine release in human monocytes infected with Francisella. In sharp contrast, we found that the highly virulent type A SCHU S4 strain of Francisella tularensis (F.t. led to a significantly lower miR-155 response than the less virulent F.n. Hence, F.n. induces miR-155 expression and leads to down-regulation of SHIP, resulting in enhanced pro-inflammatory responses. However, impaired miR-155 induction by SCHU S4 may help explain the lack of both SHIP down-regulation and pro-inflammatory response and may account for the virulence of Type A Francisella.

  16. miR-155 functions downstream of angiotensin II receptor subtype 1 and calcineurin to regulate cardiac hypertrophy.

    Science.gov (United States)

    Yang, Yong; Zhou, Yong; Cao, Zheng; Tong, Xin Zhu; Xie, Hua Qiang; Luo, Tao; Hua, Xian Ping; Wang, Han Qin

    2016-09-01

    Cardiac hypertrophy is characterized by maladaptive tissue remodeling that may lead to heart failure or sudden death. MicroRNAs (miRs) are negative regulators of angiotensin II and the angiotensin II receptor subtype 1 (AGTR1), which are two components involved in cardiac hypertrophy. In the present study, the interaction between angiotensin II receptor subtype 1 (AGTR1) signaling and miR-155 was investigated. Rat H9C2 (2-1) cardiomyocytes were transfected with miR-155 analogues or inhibitors, then stimulated with angiotensin II to induce cardiac hypertrophy. miR-155 expression was revealed to be altered following transfection with chemically-modified miR-155 analogues and inhibitors in rat cardiomyocytes. In cell cardiac hypertrophy models, the cell surface area, AGTR1, atrial natriuretic peptide and myosin heavy chain-β mRNA expression levels were revealed to be lower in cells stimulated with miR-155 analogue-transfected cells treated with angiotensin II compared with cells stimulated with angiotensin alone (PAGTR1 and suppressing the calcium signaling pathways activated by AGTR1.

  17. OncomiR addiction is generated by a miR-155 feedback loop in Theileria-transformed leukocytes.

    Science.gov (United States)

    Marsolier, Justine; Pineau, Sandra; Medjkane, Souhila; Perichon, Martine; Yin, Qinyan; Flemington, Erik; Weitzman, Matthew D; Weitzman, Jonathan B

    2013-01-01

    The intracellular parasite Theileria is the only eukaryote known to transform its mammalian host cells. We investigated the host mechanisms involved in parasite-induced transformation phenotypes. Tumour progression is a multistep process, yet 'oncogene addiction' implies that cancer cell growth and survival can be impaired by inactivating a single gene, offering a rationale for targeted molecular therapies. Furthermore, feedback loops often act as key regulatory hubs in tumorigenesis. We searched for microRNAs involved in addiction to regulatory loops in leukocytes infected with Theileria parasites. We show that Theileria transformation involves induction of the host bovine oncomiR miR-155, via the c-Jun transcription factor and AP-1 activity. We identified a novel miR-155 target, DET1, an evolutionarily-conserved factor involved in c-Jun ubiquitination. We show that miR-155 expression led to repression of DET1 protein, causing stabilization of c-Jun and driving the promoter activity of the BIC transcript containing miR-155. This positive feedback loop is critical to maintain the growth and survival of Theileria-infected leukocytes; transformation is reversed by inhibiting AP-1 activity or miR-155 expression. This is the first demonstration that Theileria parasites induce the expression of host non-coding RNAs and highlights the importance of a novel feedback loop in maintaining the proliferative phenotypes induced upon parasite infection. Hence, parasite infection drives epigenetic rewiring of the regulatory circuitry of host leukocytes, placing miR-155 at the crossroads between infection, regulatory circuits and transformation.

  18. MiR-155 Enhances Insulin Sensitivity by Coordinated Regulation of Multiple Genes in Mice

    Science.gov (United States)

    Lin, Taoyan; Lin, Xia; Chen, Li; Zeng, Hui; Han, Yanjiang; Wu, Lihong; Huang, Shun; Wang, Meng; Huang, Shenhao; Xie, Raoying; Liang, Liqi; Liu, Yu; Liu, Ruiyu; Zhang, Tingting; Li, Jing; Wang, Shengchun; Sun, Penghui; Huang, Wenhua; Yao, Kaitai; Xu, Kang; Du, Tao; Xiao, Dong

    2016-01-01

    miR-155 plays critical roles in numerous physiological and pathological processes, however, its function in the regulation of blood glucose homeostasis and insulin sensitivity and underlying mechanisms remain unknown. Here, we reveal that miR-155 levels are downregulated in serum from type 2 diabetes (T2D) patients, suggesting that miR-155 might be involved in blood glucose control and diabetes. Gain-of-function and loss-of-function studies in mice demonstrate that miR-155 has no effects on the pancreatic β-cell proliferation and function. Global transgenic overexpression of miR-155 in mice leads to hypoglycaemia, improved glucose tolerance and insulin sensitivity. Conversely, miR-155 deficiency in mice causes hyperglycemia, impaired glucose tolerance and insulin resistance. In addition, consistent with a positive regulatory role of miR-155 in glucose metabolism, miR-155 positively modulates glucose uptake in all cell types examined, while mice overexpressing miR-155 transgene show enhanced glycolysis, and insulin-stimulated AKT and IRS-1 phosphorylation in liver, adipose tissue or skeletal muscle. Furthermore, we reveal these aforementioned phenomena occur, at least partially, through miR-155-mediated repression of important negative regulators (i.e. C/EBPβ, HDAC4 and SOCS1) of insulin signaling. Taken together, these findings demonstrate, for the first time, that miR-155 is a positive regulator of insulin sensitivity with potential applications for diabetes treatment. PMID:27711113

  19. Influence of miR-155 on Cell Apoptosis in Rats with Ischemic Stroke: Role of the Ras Homolog Enriched in Brain (Rheb)/mTOR Pathway

    Science.gov (United States)

    Xing, Guoping; Luo, Zengxiang; Zhong, Chi; Pan, Xudong; Xu, Xiaowei

    2016-01-01

    Background We designed and carried out this study to examine the role of miR-155 and the Rheb/mTOR pathway in ischemic stroke. We also investigated how these two elements interact with each other and contribute to injuries resulting from ischemic stroke. Material/Methods We used both a middle cerebral artery occlusion rat model in vivo and an oxygen-glucose deprivation cell model in vitro to simulate the onset of ischemic stroke. miR-155 mimics, miR-155 inhibitors, and Rheb siRNA were transfected to alter the expression of miR-155 and Rheb. Infarct sizes were measured using magnetic resonance imaging (MRI) and triphenyltetrazolium chloride (TTC) staining; cell apoptosis rates were calculated using Annexin V-FITC/PI staining and flow cytometry. Levels of miR-155, Rheb, mTOR, and S6K were examined by RT-PCR, immunofluorescence, and western blot. We performed a luciferase activity assay so that the association between miR-155 and Rheb could be fully assessed. Results We demonstrated that miR-155 bound the 3′-UTR of Rheb and suppressed Rheb expression. As suggested by animal models, significant cerebral infarct volumes and cell apoptosis were induced by increased expression of miR-155 and decreased expression of Rheb, mTOR, and p-S6K (P<0.05). miR-155 inhibitors exhibited protective effects on ischemic stroke, including down-regulation of infarction size in cerebral tissues in vivo and reduced apoptosis of BV2 cells in vitro with increased expression of Rheb, mTOR and p-S6K (P<0.05). These protective effects could be substantially antagonized by the transfection of Rheb siRNA (P<0.05). Conclusions Inhibition of miR-155 may play protective roles in ischemic stroke by phosphorylating S6K through the Rheb/mTOR pathway. PMID:28025572

  20. Adrenaline promotes cell proliferation and increases chemoresistance in colon cancer HT29 cells through induction of miR-155

    Energy Technology Data Exchange (ETDEWEB)

    Pu, Jun [Department of General Surgery, Tangdu Hospital of the Fourth Military Medical University, Xi' an 710038 (China); Bai, Danna [Department of Cardiology, 323 Hospital of PLA, Xi' an 710054 (China); Yang, Xia [Department of Teaching and Medical Administration, Tangdu Hospital of the Fourth Military Medical University, Xi' an 710038 (China); Lu, Xiaozhao [Department of Nephrology, The 323 Hospital of PLA, Xi' an 710054 (China); Xu, Lijuan, E-mail: 13609296272@163.com [Department of Nephrology, The 323 Hospital of PLA, Xi' an 710054 (China); Lu, Jianguo, E-mail: lujianguo029@yahoo.com.cn [Department of General Surgery, Tangdu Hospital of the Fourth Military Medical University, Xi' an 710038 (China)

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer Adrenaline increases colon cancer cell proliferation and its resistance to cisplatin. Black-Right-Pointing-Pointer Adrenaline activates NF{kappa}B in a dose dependent manner. Black-Right-Pointing-Pointer NF{kappa}B-miR-155 pathway contributes to cell proliferation and resistance to cisplatin. -- Abstract: Recently, catecholamines have been described as being involved in the regulation of cancer genesis and progression. Here, we reported that adrenaline increased the cell proliferation and decreased the cisplatin induced apoptosis in HT29 cells. Further study found that adrenaline increased miR-155 expression in an NF{kappa}B dependent manner. HT29 cells overexpressing miR-155 had a higher cell growth rate and more resistance to cisplatin induced apoptosis. In contrast, HT29 cells overexpressing miR-155 inhibitor displayed decreased cell proliferation and sensitivity to cisplatin induced cell death. In summary, our study here revealed that adrenaline-NF{kappa}B-miR-155 pathway at least partially contributes to the psychological stress induced proliferation and chemoresistance in HT29 cells, shedding light on increasing the therapeutic strategies of cancer chemotherapy.

  1. Evolution of the mir-155 family and possible targets in cancers and the immune system.

    Science.gov (United States)

    Xie, Guang-Bing; Liu, Wei-Jia; Pan, Zhi-Jun; Cheng, Tian-Yin; Luo, Chao

    2014-01-01

    The mir-155 family is not only involved in a diversity of cancers, but also as a regulator of the immune system. However, the evolutionary history of this family is still unclear. The present study indicates that mir-155 evolved independently with lineage-specific gain of miRNAs. In addition, arm switching has occurred in the mir-155 family, and alternative splicing could produce two different lengths of ancestral sequences, implying the alternative splicing can also drive evolution for intragenic miRNAs. Here we screened validated target genes and immunity- related proteins, followed by analyzation of the mir-155 family function by high-throughput methods like the gene ontology (GO) and Kyoto Eneyclopedin of Genes and Genemes (KEGG) pathway enrichment analysis. The high-throughput analysis showed that the CCND1 and EGFR genes were outstanding in being significantly enriched, and the target genes cebpb and VCAM1 and the protein SMAD2 were also vital in mir-155-related immune reponse activities. Therefore, we conclude that the mir-155 family is highly conserved in evolution, and CCND1 and EGFR genes might be potential targets of mir-155 with regard to progress of cancers, while the cebpb and VCAM1 genes and the protein SMAD2 might be key factors in the mir-155 regulated immune activities.

  2. The clinical characteristics and prognostic significance of AID, miR-181b, and miR-155 expression in adult patients with de novo B-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Zhou, Guangquan; Cao, Yang; Dong, Weimin; Lin, Yan; Wang, Qi; Wu, Wei; Hua, Xiaoying; Ling, Yun; Xie, Xiaobao; Hu, Shaoyan; Cen, Jiannong; Gu, Weiying

    2017-01-31

    This study aimed to investigate clinical characteristics and prognostic significance of activation-induced cytidine deaminase (AID) gene, miR-181b and miR-155 expression in de novo adult B-cell acute lymphoblastic leukemia (B-ALL) patients. Results showed that AID and miR-155 expression were higher in B-ALL patients than healthy controls, while miR-181b expression was lower in B-ALL patients. In addition, Ph(+) B-ALLs had higher AID expression than Ph(-) B-ALLs, and its high expression was associated with BCR-ABL. Moreover, B-ALL patients with AID(high) or miR-181b(low) expression had a shorter overall survival (OS). AID(high) with miR-181b(low), AID(high) with miR-155(low), miR-181b(low), miR-155(low), AID(high) with miR-181b(low) and miR-155(low) expression were associated with shorter OS. Combination of the three molecules are more accurate predictors for unfavorable OS compared with univariate group. Therefore, AID, miR-181b and miR-155 provide clinical prognosis of adult de novo B-ALL patients and may refine their molecular risk classification.

  3. miR-155 drives telomere fragility in human breast cancer by targeting TRF1.

    Science.gov (United States)

    Dinami, Roberto; Ercolani, Cristiana; Petti, Eleonora; Piazza, Silvano; Ciani, Yari; Sestito, Rosanna; Sacconi, Andrea; Biagioni, Francesca; le Sage, Carlos; Agami, Reuven; Benetti, Roberta; Mottolese, Marcella; Schneider, Claudio; Blandino, Giovanni; Schoeftner, Stefan

    2014-08-01

    Telomeres consist of DNA tandem repeats that recruit the multiprotein complex shelterin to build a chromatin structure that protects chromosome ends. Although cancer formation is linked to alterations in telomere homeostasis, there is little understanding of how shelterin function is limited in cancer cells. Using a small-scale screening approach, we identified miR-155 as a key regulator in breast cancer cell expression of the shelterin component TERF1 (TRF1). miR-155 targeted a conserved sequence motif in the 3'UTR of TRF1, resulting in its translational repression. miR-155 was upregulated commonly in breast cancer specimens, as associated with reduced TRF1 protein expression, metastasis-free survival, and relapse-free survival in estrogen receptor-positive cases. Modulating miR-155 expression in cells altered TRF1 levels and TRF1 abundance at telomeres. Compromising TRF1 expression by elevating miR-155 increased telomere fragility and altered the structure of metaphase chromosomes. In contrast, reducing miR-155 levels improved telomere function and genomic stability. These results implied that miR-155 upregulation antagonizes telomere integrity in breast cancer cells, increasing genomic instability linked to poor clinical outcome in estrogen receptor-positive disease. Our work argued that miRNA-dependent regulation of shelterin function has a clinically significant impact on telomere function, suggesting the existence of "telo-miRNAs" that have an impact on cancer and aging.

  4. Natural functional SNPs in miR-155 alter its expression level, blood cell counts and immune responses

    Directory of Open Access Journals (Sweden)

    Congcong Li

    2016-08-01

    Full Text Available miR-155 has been confirmed to be a key factor in immune responses in humans and other mammals. Therefore, investigation of variations in miR-155 could be useful for understanding the differences in immunity between individuals. In this study, four SNPs in miR-155 were identified in mice (Mus musculus and humans (Homo sapiens. In mice, the four SNPs were closely linked and formed two miR-155 haplotypes (A and B. Ten distinct types of blood parameters were associated with miR-155 expression under normal conditions. Additionally, 4 and 14 blood parameters were significantly different between these two genotypes under normal and lipopolysaccharide (LPS stimulation conditions, respectively. Moreover, the expression levels of miR-155, the inflammatory response to LPS stimulation and the lethal ratio following Salmonella typhimurium infection were significantly increased in mice harboring the AA genotype. Further, two SNPs, one in the loop region and the other near the 3' terminal of pre-miR-155, were confirmed to be responsible for the differential expression of miR-155 in mice. Interestingly, two additional SNPs, one in the loop region and the other in the middle of miR-155*, modulated the function of miR-155 in humans. Predictions of secondary RNA structure using RNAfold showed that these SNPs affected the structure of miR-155 in both mice and humans. Our results provide novel evidence of the natural functional SNPs of miR-155 in both mice and humans, which may affect the expression levels of mature miR-155 by modulating its secondary structure. The SNPs of human miR-155 may be considered as causal mutations for some immune-related diseases in the clinic. The two genotypes of mice could be used as natural models for studying the mechanisms of immune diseases caused by abnormal expression of miR-155 in humans.

  5. Protoporphyrin Treatment Modulates Susceptibility to Experimental Autoimmune Encephalomyelitis in miR-155-Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Jinyu Zhang

    Full Text Available We previously identified heme oxygenase 1 (HO-1 as a specific target of miR-155, and inhibition of HO-1 activity restored the capacity of miR-155-/- CD4+ T cells to promote antigen-driven inflammation after adoptive transfer in antigen-expressing recipients. Protoporphyrins are molecules recognized for their modulatory effect on HO-1 expression and function. In the present study, we investigated the effect of protoporphyrin treatment on the development of autoimmunity in miR-155-deficient mice. MiR-155-mediated control of HO-1 expression in promoting T cell-driven chronic autoimmunity was confirmed since HO-1 inhibition restored susceptibility to experimental autoimmune encephalomyelitis (EAE in miR-155-deficient mice. The increased severity of the disease was accompanied by an enhanced T cell infiltration into the brain. Taken together, these results underline the importance of miR-155-mediated control of HO-1 expression in regulating the function of chronically-stimulated T cells in EAE.

  6. AAV8-mediated in vivo overexpression of miR-155 enhances the protective capacity of genetically attenuated malarial parasites.

    Science.gov (United States)

    Hentzschel, Franziska; Hammerschmidt-Kamper, Christiane; Börner, Kathleen; Heiss, Kirsten; Knapp, Bettina; Sattler, Julia M; Kaderali, Lars; Castoldi, Mirco; Bindman, Julia G; Malato, Yann; Willenbring, Holger; Mueller, Ann-Kristin; Grimm, Dirk

    2014-12-01

    Malaria, caused by protozoan Plasmodium parasites, remains a prevalent infectious human disease due to the lack of an efficient and safe vaccine. This is directly related to the persisting gaps in our understanding of the parasite's interactions with the infected host, especially during the clinically silent yet essential liver stage of Plasmodium development. Previously, we and others showed that genetically attenuated parasites (GAP) that arrest in the liver induce sterile immunity, but only upon multiple administrations. Here, we comprehensively studied hepatic gene and miRNA expression in GAP-injected mice, and found both a broad activation of IFNγ-associated pathways and a significant increase of murine microRNA-155 (miR-155), that was especially pronounced in non-parenchymal cells including liver-resident macrophages (Kupffer cells). Remarkably, ectopic upregulation of this miRNA in the liver of mice using robust hepatotropic adeno-associated virus 8 (AAV8) vectors enhanced GAP's protective capacity substantially. In turn, this AAV8-mediated miR-155 expression permitted a reduction of GAP injections needed to achieve complete protection against infectious parasite challenge from previously three to only one. Our study highlights a crucial role of mammalian miRNAs in Plasmodium liver infection in vivo and concurrently implies their great potential as future immune-augmenting agents in improved vaccination regimes against malaria and other diseases.

  7. STAT5-mediated expression of oncogenic miR-155 in cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    Kopp, Katharina L; Ralfkiaer, Ulrik; Gjerdrum, Lise Mette R

    2013-01-01

    show that malignant T cells constitutively express high levels of miR-155 and its host gene BIC (B cell integration cluster). Using ChIP-seq, we identify BIC as a target of transcription factor STAT5, which is aberrantly activated in malignant T cells and induced by IL-2/IL-15 in non-malignant T cells....... Incubation with JAK inhibitor or siRNA-mediated knockdown of STAT5 decreases BIC/miR-155 expression, whereas IL-2 and IL-15 increase their expression in cell lines and primary cells. In contrast, knockdown of STAT3 has no effect, and BIC is not a transcriptional target of STAT3, indicating that regulation...... of BIC/miR-155 expression by STAT5 is highly specific. Malignant proliferation is significantly inhibited by an antisense-miR-155 as well as by knockdown of STAT5 and BIC.   In conclusion, we provide the first evidence that STAT5 drives expression of oncogenic BIC/miR-155 in cancer. Moreover, our data...

  8. A Tiny RNA that Packs a Big Punch: The Critical Role of a Viral miR-155 Ortholog in Lymphomagenesis in Marek’s Disease

    Directory of Open Access Journals (Sweden)

    Guoqing Zhuang

    2017-06-01

    Full Text Available MicroRNAs (miRNAs are small non-coding RNAs that have been identified in animals, plants, and viruses. These small RNAs play important roles in post-transcriptional regulation of various cellular processes, including development, differentiation, and all aspects of cancer biology. Rapid-onset T-cell lymphoma of chickens, namely Marek’s disease (MD, induced by Gallid alphaherpesvirus 2 (GaHV2, could provide an ideal natural animal model for herpesvirus-related cancer research. GaHV2 encodes 26 mature miRNAs derived from 14 precursors assembled in three distinct gene clusters in the viral genome. One of the most highly expressed GaHV2 miRNAs, miR-M4-5p, shows high sequence similarity to the cellular miR-155 and the miR-K12-11 encoded by Kaposi’s sarcoma-associated herpesvirus, particularly in the miRNA “seed region.” As with miR-K12-11, miR-M4-5p shares a common set of host and viral target genes with miR-155, suggesting that they may target the same regulatory cellular networks; however, differences in regulatory function between miR-155 and miR-M4-5p may distinguish non-viral and viral mediated tumorigenesis. In this review, we focus on the functions of miR-M4-5p as the viral ortholog of miR-155 to explore how the virus mimics a host pathway to benefit the viral life cycle and trigger virus-induced tumorigenesis.

  9. Induction of immunomodulatory miR-146a and miR-155 in small intestinal epithelium of Vibrio cholerae infected patients at acute stage of cholera

    Science.gov (United States)

    Melgar, Silvia; Aung, Kyaw Min; Rahman, Arman; Qadri, Firdausi; Wai, Sun Nyunt; Shirin, Tahmina

    2017-01-01

    The potential immunomodulatory role of microRNAs in small intestine of patients with acute watery diarrhea caused by Vibrio cholerae O1 or enterotoxigenic Escherichia coli (ETEC) infection was investigated. Duodenal biopsies were obtained from study-participants at the acute (day 2) and convalescent (day 21) stages of disease, and from healthy individuals. Levels of miR-146a, miR-155 and miR-375 and target gene (IRAK1, TRAF6, CARD10) and 11 cytokine mRNAs were determined by qRT-PCR. The cellular source of microRNAs in biopsies was analyzed by in situ hybridization. The ability of V. cholerae bacteria and their secreted products to cause changes in microRNA- and mRNA levels in polarized tight monolayers of intestinal epithelial cells was investigated. miR-146a and miR-155 were expressed at significantly elevated levels at acute stage of V. cholerae infection and declined to normal at convalescent stage (Pcholerae O1 strain C6706 and clinical isolates from two study-participants, caused significant increase in miR-155 and miR-146a by the strain C6706 (Pcholera. The inducer is probably the V. cholerae bacterium. By inducing microRNAs the bacterium can limit the innate immune response of the host, including inflammation evoked by its own secreted factors, thereby decreasing the risk of being eliminated. PMID:28319200

  10. Induction of immunomodulatory miR-146a and miR-155 in small intestinal epithelium of Vibrio cholerae infected patients at acute stage of cholera.

    Science.gov (United States)

    Bitar, Aziz; De, Rituparna; Melgar, Silvia; Aung, Kyaw Min; Rahman, Arman; Qadri, Firdausi; Wai, Sun Nyunt; Shirin, Tahmina; Hammarström, Marie-Louise

    2017-01-01

    The potential immunomodulatory role of microRNAs in small intestine of patients with acute watery diarrhea caused by Vibrio cholerae O1 or enterotoxigenic Escherichia coli (ETEC) infection was investigated. Duodenal biopsies were obtained from study-participants at the acute (day 2) and convalescent (day 21) stages of disease, and from healthy individuals. Levels of miR-146a, miR-155 and miR-375 and target gene (IRAK1, TRAF6, CARD10) and 11 cytokine mRNAs were determined by qRT-PCR. The cellular source of microRNAs in biopsies was analyzed by in situ hybridization. The ability of V. cholerae bacteria and their secreted products to cause changes in microRNA- and mRNA levels in polarized tight monolayers of intestinal epithelial cells was investigated. miR-146a and miR-155 were expressed at significantly elevated levels at acute stage of V. cholerae infection and declined to normal at convalescent stage (Pcholerae O1 strain C6706 and clinical isolates from two study-participants, caused significant increase in miR-155 and miR-146a by the strain C6706 (Pcholera. The inducer is probably the V. cholerae bacterium. By inducing microRNAs the bacterium can limit the innate immune response of the host, including inflammation evoked by its own secreted factors, thereby decreasing the risk of being eliminated.

  11. Expression of miR-155 and miR-126 in situ in cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    Kopp, Katharina L; Ralfkiaer, Ulrik; Nielsen, Boye S;

    2013-01-01

    Recently, miR-155 has been implicated in cutaneous T-cell lymphoma (CTCL). Thus, elevated levels of miR-155 were observed in skin lesions from CTCL patients as judged from qPCR and micro-array analysis and aberrant, high miR-155 expression was associated with severe disease. Moreover, miR-155...... promoted proliferation of malignant T cells in vitro. Little is, however, known about which cell types express miR-155 in vivo in CTCL skin lesions. Here, we study miR-155 expression using in situ hybridization (ISH) with a miR-155 probe, a negative control (scrambled), and a miR-126 probe as a positive...... control in nine patients with mycosis fungoides, the most frequent subtype of CTCL. We provide evidence that both malignant and non-malignant T cells stain weakly to moderately positive with the miR-155 probe, but generally negative with the miR-126 and negative control probes. Reversely, endothelial...

  12. miR-155 in the progression of lung fibrosis in systemic sclerosis.

    Science.gov (United States)

    Christmann, Romy B; Wooten, Alicia; Sampaio-Barros, Percival; Borges, Claudia L; Carvalho, Carlos R R; Kairalla, Ronaldo A; Feghali-Bostwick, Carol; Ziemek, Jessica; Mei, Yu; Goummih, Salma; Tan, Jiangning; Alvarez, Diana; Kass, Daniel J; Rojas, Mauricio; de Mattos, Thiago Lemos; Parra, Edwin; Stifano, Giuseppina; Capelozzi, Vera L; Simms, Robert W; Lafyatis, Robert

    2016-07-05

    MicroRNA (miRNA) control key elements of mRNA stability and likely contribute to the dysregulated lung gene expression observed in systemic sclerosis associated interstitial lung disease (SSc-ILD). We analyzed the miRNA gene expression of tissue and cells from patients with SSc-ILD. A chronic lung fibrotic murine model was used. RNA was isolated from lung tissue of 12 patients with SSc-ILD and 5 controls. High-resolution computed tomography (HRCT) was performed at baseline and 2-3 years after treatment. Lung fibroblasts and peripheral blood mononuclear cells (PBMC) were isolated from healthy controls and patients with SSc-ILD. miRNA and mRNA were analyzed by microarray, quantitative polymerase chain reaction, and/or Nanostring; pathway analysis was performed by DNA Intelligent Analysis (DIANA)-miRPath v2.0 software. Wild-type and miR-155 deficient (miR-155ko) mice were exposed to bleomycin. Lung miRNA microarray data distinguished patients with SSc-ILD from healthy controls with 185 miRNA differentially expressed (q < 0.25). DIANA-miRPath revealed 57 Kyoto Encyclopedia of Genes and Genomes pathways related to the most dysregulated miRNA. miR-155 and miR-143 were strongly correlated with progression of the HRCT score. Lung fibroblasts only mildly expressed miR-155/miR-21 after several stimuli. miR-155 PBMC expression strongly correlated with lung function tests in SSc-ILD. miR-155ko mice developed milder lung fibrosis, survived longer, and weaker lung induction of several genes after bleomycin exposure compared to wild-type mice. miRNA are dysregulated in the lungs and PBMC of patients with SSc-ILD. Based on mRNA-miRNA interaction analysis and pathway tools, miRNA may play a role in the progression of the disease. Our findings suggest that targeting miR-155 might provide a novel therapeutic strategy for SSc-ILD.

  13. Chitosan Combined with Molecular Beacon for Mir-155 Detection and Imaging in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Hai-Zhen Zhu

    2014-09-01

    Full Text Available Lung cancer is the major cause of cancer-related deaths worldwide, thus developing effective methods for its early diagnosis is urgently needed. In recent years, microRNAs (miRNAs, miR have been reported to play important roles in carcinogenesis and have become potential biomarkers for cancer diagnosis and treatment. Molecular beacon (MB technology is a universal technology to detect DNA/RNA expression in living cells. As a natural polymers, chitosan (CS nanoparticles could be used as a carrier for safe delivery of nucleic acid. In this study, we developed a probe using nanoparticles of miR-155 MB self assembled with CS (CS-miR-155 MB to image the expression of miR-155 in cancer cells. Hybridization assay showed that the locked nucleic acid (LAN modified miR-155 MB could target miR-155 effectively and sensitively. The miR-155 MB self-assembly with CS nanoparticles formed stable complexes at the proper weight ratio. The CS nanoparticles showed higher fluorescence intensity and transfection efficiency than the lipid-based formulation transfection agent by confocal microscopy and flow cytometry analysis. The CS-MB complexes were found to be easily synthesized and exhibited strong enzymatic stability, efficient cellular uptake, high target selectivity and biocompatibility. The CS-MB complexes can also be applied in other cancers just by simply changing for a targeted miRNA highly expressed in those cancer cells. Therefore, it is a promising vehicle used for detecting miRNA expression in living cells.

  14. MicroRNA-155 in exosomes secreted from helicobacter pylori infection macrophages immunomodulates inflammatory response

    Science.gov (United States)

    Wang, Jianjun; Deng, Zhiyong; Wang, Zeyou; Wu, Jianhong; Gu, Tao; Jiang, Yibiao; Li, Guangxin

    2016-01-01

    Exosomes containing microRNA-155 act as molecule carriers during immune cell-cell communication and play an important role in the inflammatory response of H. pylori infection macrophages. Previous reports have found that miR-155 was over-expressed in H. pylori infection macrophages, but the significance of which is still unknown. In this study, we analyzed the impact of miR-155 loaded in exosomes derived from macrophages to the inflammatory response of H. pylori infection macrophages and possible mechanisms. We found that miR-155 promoted the expression of inflammatory cytokines including TNF-a, IL-6, IL-23, but also increased the expression of CD40, CD63, CD81, and MCH-I. Meanwhile, inflammatory signal pathways proteins, such as MyD88, NF-κB in H. pylori infection macrophages were down-regulated due to the over-expression of miR-155. Experiments in vitro or in vivo revealed that miR-155 promoted macrophages to inhibit or kill H. pylori by regulating the inflammatory response of cells to prevent the gastritis caused by H. pylori infection. These findings contribute to the understanding of miR-155 contained in exosomes in inflammatory responses of H. pylori infection macrophages. PMID:27725852

  15. miR-155 as a Biomarker in B-Cell Malignancies

    OpenAIRE

    Hanne Due; Pernille Svendsen; Julie Støve Bødker; Alexander Schmitz; Martin Bøgsted; Hans Erik Johnsen; Tarec Christoffer El-Galaly; Anne Stidsholt Roug; Karen Dybkær

    2016-01-01

    MicroRNAs have the potential to be useful biomarkers in the development of individualized treatment since they are easy to detect, are relatively stable during sample handling, and are important determinants of cellular processes controlling pathogenesis, progression, and response to treatment of several types of cancers including B-cell malignancies. miR-155 is an oncomiR with a crucial role in tumor initiation and development of several B-cell malignancies. The present review elucidates the...

  16. Macrophage micro-RNA-155 promotes lipopolysaccharide-induced acute lung injury in mice and rats.

    Science.gov (United States)

    Wang, Wen; Liu, Zhi; Su, Jie; Chen, Wen-Sheng; Wang, Xiao-Wu; Bai, San-Xing; Zhang, Jin-Zhou; Yu, Shi-Qiang

    2016-08-01

    Micro-RNA (miR)-155 is a novel gene regulator with important roles in inflammation. Herein, our study aimed to explore the role of miR-155 in LPS-induced acute lung injury(ALI). ALI in mice was induced by intratracheally delivered LPS. Loss-of-function experiments performed on miR-155 knockout mice showed that miR-155 gene inactivation protected mice from LPS-induced ALI, as manifested by preserved lung permeability and reduced lung inflammation compared with wild-type controls. Bone marrow transplantation experiments identified leukocytes, but not lung parenchymal-derived miR-155-promoted acute lung inflammation. Real-time PCR analysis showed that the expression of miR-155 in lung tissue was greatly elevated in wild-type mice after LPS stimulation. In situ hybridization showed that miR-155 was mainly expressed in alveolar macrophages. In vitro experiments performed in isolated alveolar macrophages and polarized bone marrow-derived macrophages confirmed that miR-155 expression in macrophages was increased in response to LPS stimulation. Conversely, miR-155 gain-of-function in alveolar macrophages remarkably exaggerated LPS-induced acute lung injury. Molecular studies identified the inflammation repressor suppressor of cytokine signaling (SOCS-1) as the downstream target of miR-155. By binding to the 3'-UTR of the SOCS-1 mRNA, miR-155 downregulated SOCS-1 expression, thus, permitting the inflammatory response during lung injury. Finally, we generated a novel miR-155 knockout rat strain and showed that the proinflammatory role of miR-155 was conserved in rats. Our study identified miR-155 as a proinflammatory factor after LPS stimulation, and alveolar macrophages-derived miR-155 has an important role in LPS-induced ALI. Copyright © 2016 the American Physiological Society.

  17. AB037. Icariside II improves human cavernous endothelial cells function by regulating miR-155/eNOS signal pathway

    Science.gov (United States)

    Guan, Ruili; Lei, Hongen; Yang, Bicheng; Li, Huixi; Wang, Lin; Guo, Yinglu; Xin, Zhongcheng

    2016-01-01

    Background To investigate the changes of miR-155/endothelial nitric oxide synthase (eNOS) signal pathway under the stimulation of age-BSA and glucose with or without icariside II (ICAII) intervention inhuman cavernous endothelial cells (HCECs). Methods Purified HCECs were first divided into three groups randomly: normal group + BSA (NC group), age-BSA + glucose group (DM group), ICAII treatment group (DM + ICAII group with different concentrations at 0.1, 1, 10 µM). Western Blot to detect the protein expression of eNOS and RAGE; real time PCR to detect the expression of miR-155 and eNOS; DAF-FM DA fluorescent probes assay and NaNO3/NaNO2 assay to detect the NO concentration. Lentivirus mediated miR-155 over-expression was constructed to observe the changes of eNOS and NO. Results The eNOS and RAGE expression in DM group is significantly reduced and increased respectively compared with that of NC group (P<0.05), while ICAII intervention could reverse this change effectively. The 10 µM of ICAII has the most powerful effect. MiR-155 has the highest fold changes among candidate miRNAs in diabetic like HCECs (P<0.05). MiR-155 increased and eNOS decreased remarkably in DM group, while ICAII intervention could inhibit the miR-155 expression, which led to the significantly higher eNOS expression and NO concentration (P<0.05). In lentivirus mediated miR-155 overexpression with or without ICAII intervention model, we found the similar trend with the above diabetic model. Conclusions MiR-155/eNOS signal pathway may be involved in the process of diabetic HCECs dysfunction. ICAII could promote the recovery of the endothelial dysfunction by regulating the miR-155/eNOS signal pathway.

  18. Study of miR-155 expression in villus tissue of patients with recurrent spontaneous abortion and its relationship with apoptosis molecules and angiogenesis molecules

    Institute of Scientific and Technical Information of China (English)

    Hong-Ying Du; Man-Zhen Zuo; Qiao-Ling Wang; Xiao-Juan Xie

    2016-01-01

    Objective:To study miR-155 expression in villus tissue of patients with recurrent spontaneous abortion and its relationship with apoptosis molecules and angiogenesis molecules.Methods:40 cases of patients with unexplained recurrent spontaneous abortion were selected as URSA group, 30 cases of normal early pregnant women receiving artificial abortion were selected as control group, and villus tissue was collected to detect expression levels of miR-155, apoptosis molecules (Bcl-2, Bcl-xl, Bax, Bad, Fas and FasL) and angiogenesis molecules (HIF-1α, VEGF and sFlt-1).Results: MiR-155 expression level in villus tissue of URSA group was significantly lower than that of control group and the more the times of abortion, the lower the miR-155 expression level; pro-apoptosis molecules Bax, Bad, Fas and FasL expression levels in villus tissue of URSA group were higher than those of control group and negatively correlated with miR-155 expression level, and anti-apoptosis genes Bcl-2 and Bcl-xl expression levels were lower than those of control group and positively correlated with miR-155 expression level; HIF-1α and VEGF expression levels in villus tissue of URSA group were lower than those of control group and positively correlated with miR-155 expression level, and sFlt-1 expression level was higher than that of control group and negatively correlated with miR-155 expression level.Conclusions:MiR-155 is lowly expressed in villus tissue of patients with recurrent spontaneous abortion, and miR-155 may be involved in the occurrence and development of the disease through regulating the expression of apoptosis molecules and angiogenesis molecules.

  19. Overexpression of miR -155 promotes proliferation and invasion of human laryngeal squamous cell carcinoma via targeting SOCS1 and STAT3.

    Directory of Open Access Journals (Sweden)

    Xu-dong Zhao

    Full Text Available MicroRNA155 plays an important role in many solid malignancies. Expression and function of miR-155 in laryngeal carcinoma have not been fully understood. This study aims to investigate the expression and function of miR-155 in laryngeal squamous cell carcinoma (LSCC, the relationship between miR-155 and its downstream target suppressor of cytokine signaling 1 (SOCS1-STAT3 pathway, and the related clinicopathological factors. Sixty-three samples of laryngeal squamous cell carcinoma and twenty-one samples of control mucosa obtained from total laryngectomy cases were analyzed using Western blot analysis and real-time PCR. Hep-2 cells were cultured and transfected with miR-155 mimic and ASO. Cell proliferation, migration and invasion assays were used to determine the role of miR-155 in regulation of LSCC growth, migration, and invasion, respectively. The expression levels of miR-155 in LSCC were significantly higher than those in the control mucosa tissues. Downregulation of SOCS1 expression and elevated expression of STAT3 were also observed in LSCC. The relevance of the three factors were statistically significant. Moreover, knockdown of miR-155 elevated SOCS1expression level, suppressed STAT3 expression, and inhibited hep-2 cells growth, migration and invasion. Whereas overexpression of miR-155 inhibited SOCS1expression, elevated STAT3 expression, and promoted hep-2 cells growth, migration and invasion. Furthermore, the miR-155 levels in T(3 T(4 stages, and poor/moderate cell differentiation were significantly higher than those in T(2 stage and higher degree of cell differentiation. The STAT3 protein in poor/moderate cell differentiation was significantly higher than those in higher degree of cell differentiation. We firstly demonstrated the aberrant expression and function of miR-155 and itsdownstream targets in LSCC. The current findings suggest that miR-155 play promotingrole during the development of LSCC, and miR-155 may be a useful marker for the prognosis and assessment of therapeutic effects.

  20. Analysis of miR-205 and miR-155 expression in the blood of breast cancer patients

    Institute of Scientific and Technical Information of China (English)

    Jingjing Liu; Qixin Mao; Yan Liu; Xiaomeng Hao; Sheng Zhang; Jin Zhang

    2013-01-01

    The purpose of this study was to identify and validate circulating microRNAs (miRNAs) in human plasma for use as breast cancer (BC) biomarkers and to analyze their relationship to clinicopathologic features and its preliminary biological function.Genome-wide expression profiling of miRNAs in BC was investigated by microarray analysis.nmiR-155 was up-regulated greater than two-fold in BC compared with Normal Adjacent Tissue (NAT),whereas let-7b,miR-381,miR-10b,miR-125a-Sp,miR-335,miR-205 and miR-145 were down-regulated greater than two-fold.Our hypothesis was that circulating miRNAs are also present and differentially expressed in the serum of BC patients compared to controls.Using real-time PCR (RT-PCR),we analyzed miR-205 and miR-155 in archived serum from 30 participants,20 with breast cancer and 10 healthy people.miR-205 was down-regulated in BC patient serum while miR-155 was up-regulated.Furthermore,we analyzed the relationship between the expression levels of these two miRNAs and the clinicopathologic parameters of BC patients.High expression of miR155 was associated with clinical stage,molecular type,Ki-67 and p53 in BC patients (P<0.05).By contrast,we found no significant correlation between miR-205 and BC patient clinicopathologic parameters.Functional analysis showed that ectopic expression of miR-205 significantly inhibits cell proliferation and promotes apoptosis.miR-205 was down-regulated and miR-155 was up-regulated in BC patient serum.miR-155 was positive correlated with clinical stage and ki-67 and negatively correlated with p53 status.

  1. Circulating levels of inflammation-associated miR-155 and endothelial-enriched miR-126 in patients with end-stage renal disease

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Honglei; Peng, Wujian; Shen, Xuemei; Huang, Yunhui; Ouyang, Xin; Dai, Yong [Clinical Medical Research Center, Second Clinical Medical College, Shenzhen People' s Hospital, Jinan University, Shenzhen, Guangdong (China)

    2012-10-19

    Circulating microRNAs (miRNAs) may represent a potential noninvasive molecular biomarker for various pathological conditions. Moreover, the detection of circulating miRNAs can provide important novel disease-related information. In particular, inflammation-associated miR-155 and endothelial-enriched miR-126 are reported to be associated with vascular homeostasis. Vascular damage is a common event described in end-stage renal disease (ESRD). We hypothesized that miR-155 and miR-126 may be detectable in the circulation and serve as potential biomarkers for risk stratification. In this study, we assessed miR-155 and miR-126 in the plasma of 30 ESRD patients and 20 healthy controls using real-time quantification RT-PCR. The circulating levels of miR-155 and miR-126 were significantly reduced in patients with ESRD compared to healthy controls. However, there was no significant difference of circulating miR-155 and miR-126 levels between prehemodialysis and posthemodialysis patients. Furthermore, both circulating miR-126 and miR-155 correlated positively with estimated glomerular filtration rate (miR-126: r = 0.383, P = 0.037; miR-155: r = 0.494, P = 0.006) and hemoglobin (miR-126: r = 0.515, P = 0.004; miR-155: r = 0.598, P < 0.001) and correlated inversely with phosphate level (miR-126: r = -0.675, P < 0.001; miR-155: r = -0.399, P = 0.029). Pearson's correlation was used to compare circulating levels of miRNAs with clinical parameters. These results suggested that circulating miR-155 and miR-126 might be involved in the development of ESRD. Further studies are needed to demonstrate the role of circulating miR-155 and miR-126 as candidate biomarkers for risk estimation.

  2. Decreased MiR-155 Level in the Peripheral Blood of Non-Alcoholic Fatty Liver Disease Patients may Serve as a Biomarker and may Influence LXR Activity

    Directory of Open Access Journals (Sweden)

    Lei Wang

    2016-11-01

    Full Text Available Background: Obesity is now a common risk factor for non-alcoholic fatty liver disease (NAFLD. Thus, it is important to explore its underlying mechanisms. Methods: Total RNA was extracted from peripheral whole blood samples from 50 NAFLD patients and 50 healthy controls. In addition, human liver specimens were obtained through liver biopsies from NAFLD patients and healthy controls. The level of miRNA was studied using real-time PCR. The expression of lipogenic genes was analyzed using western blot, and a dual luciferase reporter assay was conducted to identify the possible target gene. Adenovirus vectors were injected into the tail vein of the high fat diet (HFD-fed mice to study the role of miR-155 on lipid accumulation in vivo. Results: The level of miR-155 was markedly reduced in the livers and peripheral blood of NAFLD patients compared with healthy controls. Upregulation of miR-155 decreased intracellular lipid content and the SREBP1 and FAS protein levels, while inhibition of miR-155 enhanced the intracellular lipid content. The dual luciferase reporter assay showed that Liver X receptor (LXRα was the target gene of miR-155, and silencing miR-155 reduced the expression of SREBP1 and FAS. An in vivo study showed that upregulation of miR-155 decreased the hepatic lipid accumulation mainly by suppressing the LXRα-dependent lipogenic signaling pathway. Conclusions: In summary, decreased expression of miR-155 in the peripheral blood may be utilized as a potential novel biomarker for NAFLD screening mainly by targeting LXRα.

  3. miR-155 Over-expression Promotes Genomic Instability by Reducing High-fidelity Polymerase Delta Expression and Activating Error-prone DSB Repair

    Science.gov (United States)

    Czochor, Jennifer R.; Sulkowski, Parker; Glazer, Peter M.

    2016-01-01

    miR-155 is an oncogenic microRNA (miR) that is often over-expressed in cancer and is associated with poor prognosis. miR-155 can target several DNA repair factors including RAD51, MLH1, and MSH6, and its over-expression results in an increased mutation frequency in vitro, although the mechanism has yet to be fully understood. Here, we demonstrate that over-expression of miR-155 drives an increased mutation frequency both in vitro and in vivo, promoting genomic instability by affecting multiple DNA repair pathways. miR-155 over-expression causes a decrease in homologous recombination, but yields a concurrent increase in the error-prone non-homologous end-joining (NHEJ) pathway. Despite repressing established targets MLH1 and MSH6, the identified mutation pattern upon miR-155 over-expression does not resemble that of a mismatch repair-deficient background. Further investigation revealed that all four subunits of polymerase delta, a high-fidelity DNA replication and repair polymerase, are down-regulated at the mRNA level in the context of miR-155 over-expression. FOXO3a, a transcription factor and known target of miR-155, has one or more putative binding site(s) in the promoter of all four polymerase delta subunits. Finally, suppression of FOXO3a by miR-155 or by siRNA knockdown is sufficient to repress the expression of the catalytic subunit of polymerase delta, POLD1, at the protein level, indicating that FOXO3a contributes to the regulation of polymerase delta levels. PMID:26850462

  4. miR-155, a Modulator of FOXO3a Protein Expression, Is Underexpressed and Cannot Be Upregulated by Stimulation of HOZOT, a Line of Multifunctional Treg.

    Directory of Open Access Journals (Sweden)

    Mayuko Yamamoto

    Full Text Available MicroRNAs (miRNAs play important roles in regulating post-transcriptional gene repression in a variety of immunological processes. In particular, much attention has been focused on their roles in regulatory T (Treg cells which are crucial for maintaining peripheral tolerance and controlling T cell responses. Recently, we established a novel type of human Treg cell line, termed HOZOT, multifunctional cells exhibiting a CD4(+CD8(+ phenotype. In this study, we performed miRNA profiling to identify signature miRNAs of HOZOT, and therein identified miR-155. Although miR-155 has also been characterized as a signature miRNA for FOXP3(+ natural Treg (nTreg cells, it was expressed quite differently in HOZOT cells. Under both stimulatory and non-stimulatory conditions, miR-155 expression remained at low levels in HOZOT, while its expression in nTreg and conventional T cells remarkably increased after stimulation. We next searched candidate target genes of miR-155 through bioinformatics, and identified FOXO3a, a negative regulator of Akt signaling, as a miR-155 target gene. Further studies by gain- and loss-of-function experiments supported a role for miR-155 in the regulation of FOXO3a protein expression in conventional T and HOZOT cells.

  5. Prognostic value of miR-155 in individuals with monoclonal B-cell lymphocytosis and patients with B chronic lymphocytic leukemia.

    Science.gov (United States)

    Ferrajoli, Alessandra; Shanafelt, Tait D; Ivan, Cristina; Shimizu, Masayoshi; Rabe, Kari G; Nouraee, Nazila; Ikuo, Mariko; Ghosh, Asish K; Lerner, Susan; Rassenti, Laura Z; Xiao, Lianchun; Hu, Jianhua; Reuben, James M; Calin, Steliana; You, M James; Manning, John T; Wierda, William G; Estrov, Zeev; O'Brien, Susan; Kipps, Thomas J; Keating, Michael J; Kay, Neil E; Calin, George A

    2013-09-12

    Noncoding RNAs play a pivotal role in the pathogenesis of chronic lymphocytic leukemia (CLL). We hypothesized that microRNAs (miRs) are involved in the transition from monoclonal B-cell lymphocytosis (MBL) to CLL and tested miR-15a/16-1 cluster, miR-21, and miR-155 expression in purified B cells of normal individuals, individuals with MBL, and patients with CLL. When we analyzed 224 samples from 2 independent training and validation cohorts, we found that miR-155 was overexpressed in B cells from individuals with MBL, and even more so in B cells from patients with CLL, when compared with B cells from normal individuals. Furthermore, we were able to identify miR-155 in circulating microvesicles from both individuals with MBL and patients with CLL. Next, to examine the prognostic role of miR-155, we measured its expression level in plasma samples collected before treatment initiation in 228 patients with CLL. We found significantly higher miR-155 expression levels in patients who failed to achieve a complete response compared with those who experienced complete response. Our findings support the use of cellular and plasma levels of miR-155 as biomarkers for the risk of progression in individuals with MBL, as well as to identify patients with CLL who may not respond well to therapy.

  6. Angiotensin II type I receptor and miR-155 in endometrial cancers: synergistic antiproliferative effects of anti-miR-155 and losartan on endometrial cancer cells.

    Science.gov (United States)

    Choi, Chel Hun; Park, Young-Ae; Choi, Jung-Joo; Song, Taejong; Song, Sang Yong; Lee, Yoo-Young; Lee, Jeong-Won; Kim, Tae-Joong; Kim, Byoung-Gie; Bae, Duk-Soo

    2012-07-01

    MicroRNA-155 (miR-155) is one of the micro RNAs (miRNA) most consistently involved in neoplastic diseases, and it is known to repress the angiotensin II type 1 receptor (AGTR1). The aim of the present study was to evaluate the expressions of miR-155 and AGTR1, and to clarify the potential efficacy of anti-miR-155, alone and in combination with AGTR1 blocker losartan in endometrial cancers. Expressions of miR-155 and AGTR1 were evaluated using real-time PCR and immunohistochemistry. And the MTT assay was performed in endometrial cancer cells following anti-miR-155 and AGTR1 blocker (losartan) treatment, alone and in combination. miR-155 was over-expressed and AGTR1 was underexpressed in endometrial carcinoma tissues. AGTR1 immunoreactivity was found in six of ten (60.0%) normal endometrium, 11 of 14 (78.6%) endometrial hyperplasia, and 27 of 62 (43.5%) endometrial carcinoma tissues (P=0.051), and patients with AGTR1 expression showed trend towards improved survival after multivariate analysis (P=0.08). We checked that abolishing the function of miR-155 and AGTR1 by anti-miR-155 or losartan inhibited cell survival of endometrial carcinoma cells, respectively, and furthermore, combined treatment showed synergistic effects. In this study, we characterized the expressions of miR-155 and AGTR1 in endometrial tissues. The combined treatment with anti-miR-155 and losartan has a synergistic antiproliferative effect and an improved understanding is required to clarify whether miR-155 and AGTR1 can be used as a novel therapeutic target in endometrial cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Helicobacter pylori may induce bile reflux: link between H pylori and bile induced injury to gastric epithelium.

    Science.gov (United States)

    Ladas, S D; Katsogridakis, J; Malamou, H; Giannopoulou, H; Kesse-Elia, M; Raptis, S A

    1996-01-01

    Helicobacter pylori and duodenogastric reflux are both recognised as playing aetiological roles in chronic gastritis. This study investigated whether H pylori colonisation of the antral mucosa and duodenogastric reflux are independent phenomena or have a causal relationship. Thirty eight patients (15 men, 23 women) aged (mean (SD)) 48 (17) years participated. Each patient underwent gastroscopy. Antral biopsy specimens were taken to investigate H pylori colonisation. In addition BrIDA-99mTc/111In-DTPA scintigraphy was used to quantify duodenogastric reflux. H pylori positive patients who were found to have duodenogastric reflux were treated with amoxycillin (1 g/d) and metronidazole (1.5 g/d) for seven days and four tablets of bismuth subcitrate daily for four weeks. Follow up antral biopsies and scintigraphy were repeated at six months. Duodenogastric reflux could not be found in 18 patients, including eight (44%) who were H pylori positive. Ten of the 11 patients who had duodenogastric reflux (reflux % 11.6 (9.2)), however, were H pylori positive (chi 2 = 6.26, p = 0.01). These 10 patients were given eradication treatment. At six months, in six patients who became H pylori negative, duodenogastric reflux was significantly reduced from a pretreatment value of 14.3% to 3.3% (two tail, paired t = 2.57, p = 0.016). These data suggest that H pylori may induced duodenogastric reflux which may be important in the pathogenesis of H pylori gastritis or carcinogenesis, or both. PMID:8566844

  8. Anti-Helicobacter pylori therapy significantly reduces Helicobacter pylori-induced gastric mucosal damage in Mongolian gerbils

    Institute of Scientific and Technical Information of China (English)

    Chun-Chao Chang; Sheng-Hsuan Chen; Gi-Shih Lien; Yuarn-Jang Lee; Horng-Yuan Lou; Ching-Ruey Hsieh; Chia-Lang Fang; Shiann Pan

    2005-01-01

    AIM: To investigate the effectiveness of 4 d' anti-Helicobacter pyloritherapy on the H pylori-infected Mongolian gerbils based on physiological and pathological changes.METHODS: We used 6-wk-old male gerbils orally inoculated with H pylori (ATCC43504, 2x108 CFU/mL).Seven weeks after H pylori inoculation, the animals of study group received 4 d' anti-H pylori triple therapy (H pylorieradicated group). Seven days later, all animals of the H pylori-eradicated and control groups (H pylori-infected& H pylori-uninfected groups) were sacrificed. We examined gastric mucosal lesions macroscopically, studied gastritis microscopically and determined the stomach weight ratio, myeloperoxidase (MPO) activity and prostaglandin (PG) E2 level.RESULTS: The results showed that both macroscopic and histological gastric damages were significantly less in H pylori-eradicated group than H pylori-infected group.Stomach weight ratio, MPO activity and PGE2 levels were significantly higher in H pylori-infected group than those in the other two groups.CONCLUSION: Four days' anti-H pylori therapy was effective in the improvement of H pylori-induced gastric lesions in Mongolian gerbils.

  9. Differential Expression of miR-155 and miR-21 in Tumor and Stroma Cells in Diffuse Large B-Cell Lymphoma

    DEFF Research Database (Denmark)

    Munch-Petersen, Helga D; Ralfkiaer, Ulrik; Sjö, Lene D;

    2015-01-01

    OncomiRs miR-21 and miR-155 have been linked to lymphomagenesis, but information on their implication in diffuse large B-cell lymphoma (DLBCL) is limited. Here, we used locked nucleic acid-based in situ hybridization (ISH) detection techniques on formalin-fixed paraffin-embedded DLBCL tissue...

  10. A novel panel of serum miR-21/miR-155/miR-365 as a potential diagnostic biomarker for breast cancer

    Science.gov (United States)

    Han, Ji-Guang; Jiang, Yong-Dong; Zhang, Chun-Hui; Yang, Yan-Mei; Pang, Da; Song, Yan-Ni

    2017-01-01

    Purpose Insufficient sensitivity and specificity prevent the use of most existing biomarkers for early detection of breast cancer. Recently, it was reported that serum microRNAs (miRNAs) may be potential biomarkers in many cancer diseases. In this study, we investigated whether serum levels of 5 miRNAs including miR-21, miR-125b, miR-145, miR-155, and miR-365 could discriminate breast cancer patients and healthy controls. Methods Serum levels of miRNAs were measured by using quantitative real-time polymerase chain reaction in 99 breast cancer patients and 21 healthy controls. The abundance change of serum miRNAs were also evaluated following surgical resection in 20 breast cancer patients. Receiver operating characteristic (ROC) curve analysis was performed to assess the sensitivity and specificity of miRNAs as diagnostic biomarkers. Results Serum levels of miR-21 and miR-155 was significantly higher, while miR-365 was significantly lower in breast cancer as compared with healthy controls. The serum levels of miR-21 and miR-155 significantly decreased following surgical resection. Additionally, the serum level of miR-155 at stages I and II was significantly higher compared to stage III. The serum miR-145 level was remarkably higher in progesterone receptor (PR)-positive patients than PR-negative. The positivity of miR-21, miR-155, and miR-365 was high compared to CA 153 and CEA in breast cancer. ROC curve analyses of a combination of miR-21, miR-155, and miR-365 yielded much higher area under curve and enhanced sensitivity and specificity in comparison to each miRNA alone. Conclusion The combination of serum miR-21/miR-155/miR-365 may potentially serve as a sensitive and specific biomarker that enables differentiation of breast cancer from healthy controls. PMID:28203552

  11. 过敏性哮喘患者外周血CD4+T细胞中miR-155的表达及临床意义%Expression and clinical significance of miR-155 in peripheral blood CD4+T cells of patients with allergic asthma

    Institute of Scientific and Technical Information of China (English)

    张莺莺; 钟民; 张梦莹; 吕坤

    2012-01-01

    AIM: To investigate the expression and clinical significance of miR-155 in the peripheral blood CD4+ T cells of patients with allergic asthma. METHODS; The expression of pre-mature BIC transcript and its processed microRNA miR-155 in the CD4 + T cells from 50 patients with allergic asthma and 20 healthy individuals were measured using real-time PCR. The correlation of miR-155 expression and the disease severity of asthma was analyzed. The ability of miR-155 to influence Thl/Th2 differentiation was examined in vitro. RESULTS; The expression of pre-mature BIC and miR-155 in the CD4+ T cells of asthma patients significantly decreased compared to those in normal controls (P< 0.01). Furthermore, the expression of BIC in moderate and severe asthma patients was lower than that in normal controls (P<0. 05). Among mild, moderate, severe asthma patients, BIC expression showed no statistical significance, but miR-155 expression of severe asthma patients was lower than that in mild asthma patients (P<0.05). The expression level of miR-155 was positively correlated to FEVl/pred (%) ( P < 0. 01). miR-155 over-expression was found to promote CD4+ T cells to Thl differentiation, while of miR-155 was found to induce CCM* T cells to Th2 differentiation. CONCLUSION; The decreased expression level of miR-155 is correlated to asthma disease severity. It is suggested miR-155 plays an important role in development of asthma.%目的:探讨过敏性哮喘患者外周血CD4+T细胞中miR-155及其前体基因BIC的表达及临床意义.方法:应用实时荧光定量聚合酶链反应检测不同严重程度哮喘患者50例及健康对照20例外周血CD4+T细胞中BIC及miR-155的表达水平,并且与哮喘患者临床指标进行相关性分析;运用过表达或抑制,探讨miR-155在CD4+T细胞体外分化中的作用.结果:哮喘患者组BIC及miR-155的表达较对照组显著降低(P<0.01),中、重度哮喘患者的BIC表达均低于对照组(P<0.05),轻、中

  12. Cross-Regulation of Proinflammatory Cytokines by Interleukin-10 and miR-155 in Orientia tsutsugamushi-Infected Human Macrophages Prevents Cytokine Storm.

    Science.gov (United States)

    Tsai, Ming-Hsien; Chang, Chung-Hsing; Tsai, Rong-Kung; Hong, Yi-Ren; Chuang, Tsung-Hsien; Fan, Kan-Tang; Peng, Chi-Wen; Wu, Ching-Ying; Hsu, Wen-Li; Wang, Lih-Shinn; Chen, Li-Kuang; Yu, Hsin-Su

    2016-07-01

    Scrub typhus is caused by the obligate intracellular bacterium Orientia tsutsugamushi. Macrophages are host cells for its replication and clearance. Severe complications in patients are mainly caused by a cytokine storm resulting from overproduction of proinflammatory cytokines; nevertheless, the molecular mechanism for the occurrence remains obscure. Herein, we investigate the interactive regulation of cytokines and micro-RNA (miR) in human macrophages infected with low and high doses of O. tsutsugamushi. During low dose infection, macrophages produce high levels of IL-10 through extracellular signal-regulated kinase activation, which inhibits proinflammatory cytokine production and facilitates pathogen replication. Increasing levels of pathogen results in reduced levels of IL-10, and macrophages begin to generate high levels of proinflammatory cytokines through NF-κB activation. However, during a high dose infection, macrophages produce high levels of miR-155 to slow the proinflammatory response. The extracellular signal-regulated kinase/IL-10 axis suppresses the NF-κB/tumor necrosis factor alpha axis via activation of signal transducer and activator of transcription 3. Both IL-10 and miR-155 inhibit the NF-κB signaling pathway. Furthermore, IL-10 is a potent inhibitor of miR-155. Patients susceptible to a cytokine storm, peripheral blood mononuclear cells showed significantly lower IL-10 and miR-155 responses to O. tsutsugamushi challenge. Thus, IL-10 and miR-155 operate inhibitory mechanisms to achieve a proper defense mechanism and prevent a cytokine storm.

  13. Antagonist targeting microRNA-155 protects against lithium-pilocarpine-induced status epilepticus in C57BL/6 mice by activating brain-derived neurotrophic factor

    Directory of Open Access Journals (Sweden)

    Zhengxu eCai

    2016-05-01

    Full Text Available Epilepsy is a severe brain disorder affecting numerous patients. Recently, it is inferred that modulation of microRNA-155 (miR-155 could serve as a promising treatment of mesial temporal lobe epilepsy (MTLE. In the current study, the therapeutic potential of miR-155 antagonist against TLE was evaluated and the underlying mechanism involved in this regulation was explored. TLE model was induced by lithium-pilocarpine method. The effect of miR-155 antagonist on epilepticus symptoms of TLE mice was assessed using Racine classification and electroencephalogram (EEG recordings. The expression of brain-derived neurotrophic factor (BDNF and its association with miR-155 were also assessed with a series of experiments. Our results showed that level of miR-155 was significantly up-regulated after induction of TLE model. Based on the results of EEG and behavior analyses, seizures in mice were alleviated by miR-155 antagonist. Moreover, administration of miR-155 antagonist also significantly increased the level of BDNF. The results of dual luciferase assay and western blotting showed that miR-155 antagonist exerted its action on status epilepticus by directly regulating the activity of BDNF. Taken all the information together, our results demonstrated that miR-155 antagonist might firstly induce the expression of BDNF, which then contributed to the alleviation of epilepsy in the current study.

  14. Transcriptomics identified a critical role for Th2 cell-intrinsic miR-155 in mediating allergy and antihelminth immunity.

    Science.gov (United States)

    Okoye, Isobel S; Czieso, Stephanie; Ktistaki, Eleni; Roderick, Kathleen; Coomes, Stephanie M; Pelly, Victoria S; Kannan, Yashaswini; Perez-Lloret, Jimena; Zhao, Jimmy L; Baltimore, David; Langhorne, Jean; Wilson, Mark S

    2014-07-29

    Allergic diseases, orchestrated by hyperactive CD4(+) Th2 cells, are some of the most common global chronic diseases. Therapeutic intervention relies upon broad-scale corticosteroids with indiscriminate impact. To identify targets in pathogenic Th2 cells, we took a comprehensive approach to identify the microRNA (miRNA) and mRNA transcriptome of highly purified cytokine-expressing Th1, Th2, Th9, Th17, and Treg cells both generated in vitro and isolated ex vivo from allergy, infection, and autoimmune disease models. We report here that distinct regulatory miRNA networks operate to regulate Th2 cells in house dust mite-allergic or helminth-infected animals and in vitro Th2 cells, which are distinguishable from other T cells. We validated several miRNA (miR) candidates (miR-15a, miR-20b, miR-146a, miR-155, and miR-200c), which targeted a suite of dynamically regulated genes in Th2 cells. Through in-depth studies using miR-155(-/-) or miR-146a(-/-) T cells, we identified that T-cell-intrinsic miR-155 was required for type-2 immunity, in part through regulation of S1pr1, whereas T-cell-intrinsic miR-146a was required to prevent overt Th1/Th17 skewing. These data identify miR-155, but not miR-146a, as a potential therapeutic target to alleviate Th2-medited inflammation and allergy.

  15. Probiotic BIFICO cocktail ameliorates Helicobacter pylori induced gastritis.

    Science.gov (United States)

    Yu, Hong-Jing; Liu, Wei; Chang, Zhen; Shen, Hui; He, Li-Juan; Wang, Sha-Sha; Liu, Lu; Jiang, Yuan-Ying; Xu, Guo-Tong; An, Mao-Mao; Zhang, Jun-Dong

    2015-06-07

    To determine the protective effect of triple viable probiotics on gastritis induced by Helicobacter pylori (H. pylori) and elucidate the possible mechanisms of protection. Colonization of BIFICO strains in the mouse stomach was determined by counting colony-forming units per gram of stomach tissue. After treatment with or without BIFICO, inflammation and H. pylori colonization in the mouse stomach were analyzed by hematoxylin and eosin and Giemsa staining, respectively. Cytokine levels were determined by enzyme-linked immunosorbent assay and Milliplex. The activation of nuclear factor (NF)-κB and MAPK signaling in human gastric epithelial cells was evaluated by Western blot analysis. Quantitative reverse transcription-polymerase chain reaction was used to quantify TLR2, TLR4 and MyD88 mRNA expression in the mouse stomach. We demonstrated that BIFICO, which contains a mixture of Enterococcus faecalis, Bifidobacterium longum and Lactobacillus acidophilus, was tolerant to the mouse stomach environment and was able to survive both the 8-h and 3-d courses of administration. Although BIFICO treatment had no effect on the colonization of H. pylori in the mouse stomach, it ameliorated H. pylori-induced gastritis by significantly inhibiting the expression of cytokines and chemokines such as TNF-α, IL-1β, IL-10, IL-6, G-CSF and MIP-2 (P gastritis by inhibiting the inflammatory response in gastric epithelial cells.

  16. Screening Helicobacter pylori genes induced during infection of mouse stomachs

    Institute of Scientific and Technical Information of China (English)

    Aparna Singh; Nathaniel Hodgson; Ming Yan; Jungsoo Joo; Lei Gu; Hong Sang; Emmalena Gregory-Bryson

    2012-01-01

    AIM:To investigate the effect of in vivo environment on gene expression in Helicobacter pylori (H.pylori) as it relates to its survival in the host.METHODS:In vivo expression technology (IVET) systems are used to identify microbial virulence genes.We modified the IVET-transcriptional fusion vector,pIVET8,which uses antibiotic resistance as the basis for selection of candidate genes in host tissues to develop two unique IVET-promoter-screening vectors,pIVET11 and pIVET12.Our novel IVET systems were developed by the fusion of random Sau3A DNA fragments of H.pylori and a tandem-reporter system of chloramphenicol acetyltransferase and beta-galactosidase.Additionally,each vector contains a kanamycin resistance gene.We used a mouse macrophage cell line,RAW 264.7 and mice,as selective media to identify specific genes that H.pylori expresses in vivo.Gene expression studies were conducted by infecting RAW 264.7 cells with H.pylori.This was followed by real time polymerase chain reaction (PCR) analysis to determine the relative expression levels of in vivo induced genes.RESULTS:In this study,we have identified 31 in vivo induced (ivi) genes in the initial screens.These 31 genes belong to several functional gene families,including several well-known virulence factors that are expressed by the bacterium in infected mouse stomachs.Virulence factors,vacA and cagA,were found in this screen and are known to play important roles in H.pylori infection,colonization and pathogenesis.Their detection validates the efficacy of these screening systems.Some of the identified ivi genes have already been implicated to play an important role in the pathogenesis of H.pylori and other bacterial pathogens such as Escherichia coli and Vibrio cholerae.Transcription profiles of all ivi genes were confirmed by real time PCR analysis of H.pylori RNA isolated from H.pylori infected RAW 264.7 macrophages.We compared the expression profile of H.pylori and RAW 264.7 coculture with that of H.pylori only

  17. Signal transducer and activator of transcription-3 induces microRNA-155 expression in chronic lymphocytic leukemia.

    Directory of Open Access Journals (Sweden)

    Ping Li

    Full Text Available MicroRNA (miR abnormalities play a key role in the pathogenesis of chronic lymphocytic leukemia (CLL. High levels of miR-155 have been detected in human neoplasms, and overexpression of miR-155 has been found to induce lymphoma in mice. High levels of miR-155 were detected in CLL cells and STAT3, which is known to induce miR-21 and miR-181b-1 expression, is constitutively activated in CLL. Given these findings, we hypothesized that STAT3 induces miR-155. Sequence analysis revealed that the miR-155 promoter harbors two putative STAT3 binding sites. Therefore, truncated miR-155 promoter constructs and STAT3 small interfering RNA (siRNA were co-transfected into MM1 cells. Of the two putative binding sites, STAT3-siRNA reduced the luciferase activity of the construct containing the 700-709 bp STAT3 binding site, suggesting that this site is involved in STAT3-induced transcription. Electrophoretic mobility shift assay confirmed that STAT3 bound to the miR-155 promoter in CLL cells, and chromatin immunoprecipitation and luciferase assay confirmed that STAT3 bound to the 700-709 bp but not the 615-624 bp putative STAT3 binding site in CLL cells. Finally, STAT3-small hairpin RNA downregulated miR-155 gene expression, suggesting that constitutively activated STAT3 binds to the miR-155 gene promoter. Together, these results suggest that STAT3 activates miR-155 in CLL cells.

  18. A polymorphic miR-155 binding site in AGTR1 is associated with cardiac hypertrophy in Friedreich ataxia.

    Science.gov (United States)

    Kelly, Matthew; Bagnall, Richard D; Peverill, Roger E; Donelan, Lesley; Corben, Louise; Delatycki, Martin B; Semsarian, Christopher

    2011-11-01

    Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative condition with a heterogeneous cardiac phenotype caused primarily by an expanded GAA trinucleotide repeat in the frataxin gene (FXN). FXN is important in mitochondrial iron efflux, sensitivity to oxidative stress, and cell death. The number of GAA repeats on the smaller FXN allele (GAA1) only accounts for a portion of the observed variability in cardiac phenotype. Genetic modifying factors, such as single nucleotide polymorphisms (SNPs) in genes of the Renin-Angiotensin-Aldosterone system (RAAS), may contribute to phenotype variability. This study investigated genetic variability in the angiotensin-II type-1 receptor (AGTR1), angiotensin-converting enzyme (ACE), and ACE2 genes as cardiac phenotype modifying factors in FRDA patients. Comprehensive review of the AGTR1, ACE and ACE2 genes identified twelve haplotype tagging SNPs. Correlation of these SNPs with left ventricular internal diameter in diastole (LVIDd), interventricular septal wall thickness (SWT) and left ventricular mass (LVM) was examined in a large Australian FRDA cohort (n=79) with adjustments performed for GAA repeats, age, sex, body surface area and diastolic blood pressure. A significant inverse relationship was observed between GAA1 and LVIDd (p=0.010) but not with SWT or LVM after adjustment for covariates. The AGTR1 polymorphism rs5186 was more common in FRDA patients than in a control population (p=0.002). Using a recessive model of inheritance, the C allele of rs5186 was associated with a significant increase in SWT (p=0.003) and LVM (p=0.001). This functional polymorphism increases expression of AGTR1 by altering the binding site for miR-155, a regulatory microRNA. No significant associations with left ventricular structure were observed for the remaining RAAS polymorphisms. The AGTR1 polymorphism rs5186 appears to modify the FRDA cardiac phenotype independently of GAA1. This study supports the role of RAAS polymorphisms as modifiers of cardiac phenotype in FRDA patients. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Helicobacter pylori environmental interactions: effect of acidic conditions on H. pylori-induced gastric mucosal interleukin-8 production

    Science.gov (United States)

    Choi, Il Ju; Fujimoto, Saori; Yamauchi, Kazuyoshi; Graham, David Y.; Yamaoka, Yoshio

    2010-01-01

    Summary To explore the interactions between the host, environment and bacterium responsible for the different manifestations of Helicobacter pylori infection, we examined the effect of acidic conditions on H. pylori-induced interleukin (IL)-8 expression. AGS gastric epithelial cells were exposed to acidic pH and infected with H. pylori [wild-type strain, its isogenic cag pathogenicity island (PAI) mutant or its oipA mutant]. Exposure of AGS cells to acidic pH alone did not enhance IL-8 production. However, following exposure to acidic conditions, H. pylori infection resulted in marked enhancement of IL-8 production which was independent of the presence of the cag PAI and OipA, indicating that H. pylori and acidic conditions act synergistically to induce gastric mucosal IL-8 production. In neutral pH environments H. pylori-induced IL-8 induction involved the NF-κB pathways, the extracellular signal-regulated kinase (ERK)→ c-Fos/c-Jun→activating protein (AP-1) pathways, JNK→c-Jun→AP-1 pathways and the p38 pathways. At acidic pH H. pylori-induced augmentation of IL-8 production involved markedly upregulated the NF-κB pathways and the ERK→c-Fos→AP-1 pathways. In contrast, activation of the JNK→c-Jun→AP-1 pathways and p38 pathways were pH independent. These results might explain the clinical studies in which patients with duodenal ulcers had higher levels of IL-8 in the antral gastric mucosa than patients with simple H. pylori gastritis. PMID:17517062

  20. Streptococcus mitis induces conversion of Helicobacter pylori to coccoid cells during co-culture in vitro.

    Directory of Open Access Journals (Sweden)

    Yalda Khosravi

    Full Text Available Helicobacter pylori (H. pylori is a major gastric pathogen that has been associated with humans for more than 60,000 years. H. pylori causes different gastric diseases including dyspepsia, ulcers and gastric cancers. Disease development depends on several factors including the infecting H. pylori strain, environmental and host factors. Another factor that might influence H. pylori colonization and diseases is the gastric microbiota that was overlooked for long because of the belief that human stomach was a hostile environment that cannot support microbial life. Once established, H. pylori mainly resides in the gastric mucosa and interacts with the resident bacteria. How these interactions impact on H. pylori-caused diseases has been poorly studied in human. In this study, we analyzed the interactions between H. pylori and two bacteria, Streptococcus mitis and Lactobacillus fermentum that are present in the stomach of both healthy and gastric disease human patients. We have found that S. mitis produced and released one or more diffusible factors that induce growth inhibition and coccoid conversion of H. pylori cells. In contrast, both H. pylori and L. fermentum secreted factors that promote survival of S. mitis during the stationary phase of growth. Using a metabolomics approach, we identified compounds that might be responsible for the conversion of H. pylori from spiral to coccoid cells. This study provide evidences that gastric bacteria influences H. pylori physiology and therefore possibly the diseases this bacterium causes.

  1. miR-155在肾结石患者血清和尿液中的表达及其临床意义%Expression and its clinical significance of miR-155 in serum and urine from patients with nephrolithiasis

    Institute of Scientific and Technical Information of China (English)

    胡洋洋; 李妍; 李伟; 牛晓振; 彭波; 刘敏

    2015-01-01

    目的:血液和尿液中的miRNAs可能存在一种潜在的无创的能够预测慢性肾脏疾病的生物学标志物,在本研究中,我们将会研究肾结石患者血清和尿液中miR-155的表达水平.方法:选取2011年 8月~2012年8月间同济大学上海市第十人民医院泌尿外科收治的60例肾结石患者,以同期50例健康体检者作为对照,应用实时荧光定量PCR技术检测并比较肾结石患者和健康体检者血清和尿液miR-155的表达水平.同时计算出肾小球滤过率估算值(estimated glomerular filtration,eGFR),通过简单的回归分析,分析miR-155/eGFR 及miR-155/CRP表达水平之间的相关关系.结果: 肾结石患者血清和尿液miR-155的表达水平均显著高于对照组.eGFR与尿液中miR-155的表达水平呈负相关;CRP与尿液中miR-155的表达水平呈正相关.尿液中miR-155的表达水平同白细胞介素(IL)-1β、 IL-6和肿瘤坏死因子(TNF)-α的表达水平呈负相关,但同正常T细胞表达分泌的活性调节因子(regulated upon activation normal T-cell expression and secreted,RANTES)的表达水平呈正相关.结论:肾结石患者血清和尿液中miR-155的表达水平明显升高, miR-155表达水平的上调与eGFR下降和CRP升高有关.我们的研究结果表明miR-155通过调节炎症因子表达在肾结石的病理生理学中扮演重要的角色,有可能成为预测肾结石发病的生物学标志物.%Objective: hTere may be a potential noninvasive biomarker in miRNAs of both serum and urine, which could predict the chronic kidney disease. In the present study, we will investigate the expression of miR-155 in serum and urine of nephrolithiasis and its clinical signiifcance.Methods: Collected 60 cases blood and urine specimens of patients with nephrolithiasis from August 2011 to August 2012, and collected 50 cases blood and urine specimens of healthy volunteers in comparison. Real time quantity PCR was used to detect the expression of miR-155 in those specimens, and we compare the levels of miR-155 of nephrolithiasis and controls. Estimated glomerular ifltration (eGFR) was calculated at the same time, then analyzed the correlations of miR-155/eGFR and miR-155/CRP levels by simple regression analysis.Results:The expression levels of miR-155 in serum and urine were significance higher in patients with nephrolithiasis than controls. The miR-155 levels inversely correlated with eGFR, and positively correlated with CRP. hTe urinary miR-155 levels signiifcantly and inversely correlated with urinary interleukin(IL)-1β, IL-6 and tumor necrosis factor (TNF)-α levels, but signiifcantly and positively correlated with regulated upon activation, normal T-cell expression, and secreted (RANTES) levels. Conclusion:hTe expression levels of miR-155 in serum and urine of nephrolithiasis patients were signiifcantly elevated, and the elevated levels of miR-155 were correlated with the decrease of eGFR and increase of CRP. Our study suggests miR-155 may play an important role in the pathophysiology of nephrolithiasis, which may be used as a potential predictive biomarker of nephrolithiasis.

  2. MicroRNAs 142-3p, miR-155 and miR-203 Are Deregulated in Gastric MALT Lymphomas Compared to Chronic Gastritis.

    Science.gov (United States)

    Fernández, Concepción; Bellosillo, Beatriz; Ferraro, Mariana; Seoane, Agustín; Sánchez-González, Blanca; Pairet, Silvia; Pons, Aina; Barranco, Luis; Vela, María Carmen; Gimeno, Eva; Colomo, Lluís; Besses, Carles; Navarro, Alfons; Salar, Antonio

    2017-01-02

    Over the last years, our knowledge on pathogenesis of gastric MALT lymphoma has greatly improved, but its morphological diagnosis is still hampered by overlapping histological features with advanced chronic gastritis. MicroRNAs are deregulated in lymphomas, but their role and usefulness in gastric MALT lymphoma has not been extensively investigated. We analyzed the expression of 384 miRNAs using TaqMan microRNA assay in a training series of 10 gastric MALT lymphomas, 3 chronic gastritis and 2 reactive lymph nodes. Then, significantly deregulated miRNAs were individually assessed by real-time PCR in a validation series of 16 gastric MALT lymphomas and 12 chronic gastritis. Gastric MALT lymphoma is characterized by a specific miRNA expression profile. Among the differentially expressed miRNAs, a significant overexpression of miR-142-3p and miR-155 and down-regulation of miR-203 was observed in gastric MALT lymphoma when compared to chronic gastritis. miR-142-3p, miR-155 and miR-203 expression levels might be helpful biomarkers for the differential diagnosis between gastric MALT lymphomas and chronic gastritis. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  3. miR-155 Controls Lymphoproliferation in LAT Mutant Mice by Restraining T-Cell Apoptosis via SHIP-1/mTOR and PAK1/FOXO3/BIM Pathways.

    Directory of Open Access Journals (Sweden)

    Alexandre K Rouquette-Jazdanian

    Full Text Available Linker for Activation of T cells (LAT is an adapter protein that is essential for T cell function. Knock-in mice with a LAT mutation impairing calcium flux develop a fatal CD4+ lymphoproliferative disease. miR-155 is a microRNA that is correlated with hyperproliferation in a number of cancers including lymphomas and leukemias and is overexpressed in mutant LAT T cells. To test whether miR-155 was merely indicative of T cell activation or whether it contributes to lymphoproliferative disease in mutant LAT mice, we interbred LAT mutant and miR-155-deficient mice. miR-155 deficiency markedly inhibited lymphoproliferative disease by stimulating BIM-dependent CD4+ T cell apoptosis, even though ERK activation and T cell proliferation were increased in double mutant CD4+ T cells. Bim/Bcl2l11 expression is activated by the forkhead transcription factor FOXO3. Using miR-155-deficient, LAT mutant T cells as a discovery tool, we found two connected pathways that impact the nuclear translocation and activation of FOXO3 in T cells. One pathway is mediated by the inositide phosphatase SHIP-1 and the serine/threonine kinases AKT and PDK1. The other pathway involves PAK1 and JNK kinase activation. We define crosstalk between the two pathways via the kinase mTOR, which stabilizes PAK1. This study establishes a role for PAK1 in T cell apoptosis, which contrasts to its previously identified role in T cell proliferation. Furthermore, miR-155 regulates the delicate balance between PAK1-mediated proliferation and apoptosis in T cells impacting lymphoid organ size and function.

  4. Whole transcriptome analysis reveals dysregulated oncogenic lncRNAs in natural killer/T-cell lymphoma and establishes MIR155HG as a target of PRDM1.

    Science.gov (United States)

    Baytak, Esra; Gong, Qiang; Akman, Burcu; Yuan, Hongling; Chan, Wing C; Küçük, Can

    2017-05-01

    Natural killer/T-cell lymphoma is a rare but aggressive neoplasm with poor prognosis. Despite previous reports that showed potential tumor suppressors, such as PRDM1 or oncogenes associated with the etiology of this malignancy, the role of long non-coding RNAs in natural killer/T-cell lymphoma pathobiology has not been addressed to date. Here, we aim to identify cancer-associated dysregulated long non-coding RNAs and signaling pathways or biological processes associated with these long non-coding RNAs in natural killer/T-cell lymphoma cases and to identify the long non-coding RNAs transcriptionally regulated by PRDM1. RNA-Seq analysis revealed 166 and 66 long non-coding RNAs to be significantly overexpressed or underexpressed, respectively, in natural killer/T-cell lymphoma cases compared with resting or activated normal natural killer cells. Novel long non-coding RNAs as well as the cancer-associated ones such as SNHG5, ZFAS1, or MIR155HG were dysregulated. Interestingly, antisense transcripts of many growth-regulating genes appeared to be transcriptionally deregulated. Expression of ZFAS1, which is upregulated in natural killer/T-cell lymphoma cases, showed association with growth-regulating pathways such as stabilization of P53, regulation of apoptosis, cell cycle, or nuclear factor-kappa B signaling in normal and neoplastic natural killer cell samples. Consistent with the tumor suppressive role of PRDM1, we identified MIR155HG and TERC to be transcriptionally downregulated by PRDM1 in two PRDM1-null NK-cell lines when it is ectopically expressed. In conclusion, this is the first study that identified long non-coding RNAs whose expression is dysregulated in natural killer/T-cell lymphoma cases. These findings suggest that ZFAS1 and other dysregulated long non-coding RNAs may be involved in natural killer/T-cell lymphoma pathobiology through regulation of cancer-related genes, and loss-of-PRDM1 expression in natural killer/T-cell lymphomas may contribute to

  5. Helicobacter pylori induces cell migration and invasion through casein kinase 2 in gastric epithelial cells.

    Science.gov (United States)

    Lee, Yeo Song; Lee, Do Yeon; Yu, Da Yeon; Kim, Shin; Lee, Yong Chan

    2014-12-01

    Chronic infection with Helicobacter pylori (H. pylori) is causally linked with gastric carcinogenesis. Virulent H. pylori strains deliver bacterial CagA into gastric epithelial cells. Induction of high motility and an elongated phenotype is considered to be CagA-dependent process. Casein kinase 2 plays a critical role in carcinogenesis through signaling pathways related to the epithelial mesenchymal transition. This study was aimed to investigate the effect of H. pylori infection on the casein kinase 2-mediated migration and invasion in gastric epithelial cells. AGS or MKN28 cells as human gastric epithelial cells and H. pylori strains Hp60190 (ATCC 49503, CagA(+)) and Hp8822 (CagA(-)) were used. Cells were infected with H. pylori at multiplicity of infection of 100 : 1 for various times. We measured in vitro kinase assay to examine casein kinase 2 activity and performed immunofluorescent staining to observe E-cadherin complex. We also examined β-catenin transactivation through promoter assay and MMP7 expression by real-time PCR and ELISA. H. pylori upregulates casein kinase 2 activity and inhibition of casein kinase 2 in H. pylori-infected cells profoundly suppressed cell invasiveness and motility. We confirmed that casein kinase 2 mediates membranous α-catenin depletion through dissociation of the α-/β-catenin complex in H. pylori-infected cells. We also found that H. pylori induces β-catenin nuclear translocation and increases MMP7 expressions mediated through casein kinase 2. We show for the first time that CagA(+) H. pylori upregulates cellular invasiveness and motility through casein kinase 2. The demonstration of a mechanistic interplay between H. pylori and casein kinase 2 provides important insights into the role of CagA(+) H. pylori in the gastric cancer invasion and metastasis. © 2014 John Wiley & Sons Ltd.

  6. Helicobacter pylori infection induces genetic instability of nuclear and mitochondrial DNA in gastric cells

    DEFF Research Database (Denmark)

    Machado, Ana Manuel Dantas; Figueiredo, Ceu; Touati, Eliette

    2009-01-01

    of genetic instabilities in the nuclear and mitochondrial DNA (mtDNA) were examined. EXPERIMENTAL DESIGN: We observed the effects of H. pylori infection on a gastric cell line (AGS), on C57BL/6 mice, and on individuals with chronic gastritis. In AGS cells, the effect of H. pylori infection on base excision...... cells and chronic gastritis tissue were determined by PCR, single-stranded conformation polymorphism, and sequencing. H. pylori vacA and cagA genotyping was determined by multiplex PCR and reverse hybridization. RESULTS: Following H. pylori infection, the activity and expression of base excision repair...... and MMR are down-regulated both in vitro and in vivo. Moreover, H. pylori induces genomic instability in nuclear CA repeats in mice and in mtDNA of AGS cells and chronic gastritis tissue, and this effect in mtDNA is associated with bacterial virulence. CONCLUSIONS: Our results suggest that H. pylori...

  7. Ultrasensitive photoelectrochemical aptasensing of miR-155 using efficient and stable CH3NH3PbI3 quantum dots sensitized ZnO nanosheets as light harvester.

    Science.gov (United States)

    Pang, Xuehui; Qi, Jianni; Zhang, Yong; Ren, Yangyang; Su, Minhui; Jia, Baoxiu; Wang, Yaoguang; Wei, Qin; Du, Bin

    2016-11-15

    An ultrasensitive photoelectrochemical (PEC) aptasensor based on a novel signal amplification strategy was developed for the quantitative determination of microRNA (miR)-155. CH3NH3PbI3 quantum dots (QDs) functionalized ZnO nanosheets (NSs) were employed as the light harvester. Owing to the synergetic effect between CH3NH3PbI3 QDs and ZnO NSs, ZnO@CH3NH3PbI3 can provide an obviously increasing PEC signal by forming the heterojunction. Due to the larger steric hindrance, the sensitive decrease of the PEC signal can be achieved by the specific recognition between the primers and ssDNA of miR-155. In this sense, this developed aptasensor can achieve a high sensitivity (especially in the presence of the low concentrations of miR-155) and a wide detection range (0.01fmol/L to 20,000pmol/L). Under the optimal conditions, the proposed aptasensor offered an ultrasensitive and specific determination of miR-155 down to 0.005fmol/L. This aptassay method would open up a new promising platform at ultralow levels for early diagnose of different miRNA.

  8. miR-21 and miR-155 in the regulation of TGF-β1/SMAD signaling pathway of the line breast cancer cells with different metastatic potential

    Directory of Open Access Journals (Sweden)

    Z. N. Nikiphorova

    2015-01-01

    Full Text Available Breast cancer (ВС is the most common form of cancer, leading to high mortality rates among women worldwide. Metastasis is the main cause of fatal outcomes in ВС. In this regard, of particular interest takes the study of molecular mechanisms of epithelial-mesenchymal transition (EMT. In the EMT processes involved in TGF-β1/SMAD-signaling pathway through the regulation of which can affect the processes of metastasis in ВС. In this study we have analyzed changes of mRNA expression of the mRNA SMADs, miR-21, and miR-155 of the tumor ВС cells with different metastatic potential MCF-7, BT-474, ZR-75-1. High expression of miR-21 was detected in all the tumor cell lines (MCF-7, ZR-75-1 and BT-474. In the ВС cell lines, the expression level of miR-155 was significantly lower than that of miR-21. Analysis of mRNA expression has clearly shown impairments of intracellular mechanisms of regulation of SMAD2, SMAD4, SMAD7 in ВС. Investigated the correlation of expression of miR-21 and miR-155 regulation of SMADs in TGF-β1/SMAD signaling pathway in three carcinomas lines of the human breast with different metastatic potential (MCF-7, ZR-75-1, BT-474. A significant inverse correlation was observed between SMAD4 and miR-155 in MCF-7 cells. Inverse correlation between the expression of SMAD2, SMAD4, SMAD7 and miR-155; miR21 was found in the BT-474 cells. The results obtained in this study showed that miR-21 and miR-155 regulate activity of several genes SMAD2, SMAD4, SMAD7 in the tumor cell ZR-75-1 and on some genes they exhibited a cumulative effect. It should be noted that the miR-155 and miR-21 in various degrees influenced the expression of SMAD2, SMAD4, SMAD7, blocking the work of these genes and, thereby exacerbating the progression and degree of malignancy of ВС cells human; in some cases their effects on individual genes were cumulative. 

  9. Relationship between Helicobacter pylori infection and vomiting induced by gastrointestinal cancer chemotherapy.

    Science.gov (United States)

    Yao, Yiwei; Ji, Chushu; He, Yifu; Pan, Yueyin

    2017-07-01

    Nausea and vomiting are the most common adverse reactions to chemotherapy. To discuss the relationship between Helicobacter pylori and chemotherapy-induced nausea and vomiting (CINV). A total of 112 patients with malignant tumours of the gastrointestinal tract was selected. Based on the 14C-urea breath test results, the patients were divided into H. pylori-positive (n = 59) and H. pylori-negative (n = 53) groups. Both groups received prophylactic antiemetic treatment during chemotherapy. The incidence of nausea and vomiting and their effects on the patients' life functions was recorded using the Multinational Association of Supportive Care in Cancer (MASCC) Antiemetic Tool (MAT) and the Functional Living Index Emesis (FLIE) from 0-120 h after chemotherapy. Records of the H. pylori-positive and H. pylori-negative groups were compared. The rates of nausea and vomiting remission were higher in the H. pylori -negative group than in the H. pylori -positive group. The proportions of no effect in daily life (NIDL) patients in the nausea and vomiting section were 73.4 and 75.5% in the H. pylori -negative group respectively. There was a higher proportion of NIDL patients in the H. pylori -negative group than in the H. pylori -positive group (P pylori infection was a factor affecting the nausea scores on the FLIE (odds ratio = 0.757, 95% confidence interval 0.597-0.960, P = 0.021). H. pylori infection in patients with cancer may be a factor that increases CINV. © 2017 Royal Australasian College of Physicians.

  10. Early apoptosis of monocytes induced by Helicobacter pylori infection through multiple pathways.

    Science.gov (United States)

    Zhang, Ying; Sun, Hui; Zhao, Huilin; Chen, Xingxing; Li, Jiaojiao; Li, Boqing

    2017-08-01

    Only a small percentage of people infected with Helicobacter pylori (H. pylori) will develop overt chronic gastric diseases. To understand the pathological mechanism, the action of H. pylori on monocyte apoptosis was detected. H. pylori co-culturing with peripheral blood monocytes, THP-1 or U937 cells result in early apoptosis at 6, 12, and 24 h after infection. The phosphorylated Bad and JNK were increased, and Bcl-2 was declined at 6, 12, and 24 h in peripheral blood monocytes after H. pylori infection. The phosphorylated Akt was augmented at 6 and 12 h post-infection. A slow apoptotic response was induced by H. pylori via Bad and Bcl-2 regulators, activated caspase-8 and caspase-9, and JNK at 24 h in THP-1 cells. Meanwhile, only Bad and JNK were involved in regulating U937 cells apoptosis at 24 h after infection. These results supported a novel mechanism of H. pylori escaping from monocytes by upregulation of early apoptosis and inhibition of late apoptosis. The differences among the three cells may reveal why H. pylori-derived disease occurs in relatively few people and provide a pathological mechanism whereby a treatment for H. pylori-derived disease may be developed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. A Role for MicroRNA-155 Expression in Microenvironment Associated to HPV-Induced Carcinogenesis in K14-HPV16 Transgenic Mice

    Science.gov (United States)

    Paiva, Isabel; Gil da Costa, Rui M.; Ribeiro, Joana; Sousa, Hugo; Bastos, Margarida; Rocha, Ana Faustino Carlos; Oliveira, Paula A; Medeiros, Rui

    2015-01-01

    Human Papillomavirus cause a number of diseases most notably cervical cancer. K14-HPV16 transgenic mice expressing the HPV16 early genes in squamous epithelial cells provide a suitable experimental model for studying these diseases. MicroRNAs are small non-coding RNAs that play an important role in regulating gene expression and have been suggested to play an important role in cancer development. The role of miR-155 in cancer remains controversial and there is limited evidence linking this miRNA to HPV- associated diseases. We hypothesized that miR-155 expression modulates each tissue’s susceptibility to develop HPV-associated carcinogenesis. In this study, we analyzed miR-155 expression in ear and chest skin samples from 22-26 weeks old, female K14-HPV16 transgenic (HPV16+/-) and wild-type (HPV-/-) mice. Among wild-type mice the expression of miR-155 was lower in ear skin compared with chest skin (p = 0.028). In transgenic animals, in situ carcinoma was present in all ear samples whereas chest tissues only showed epidermal hyperplasia. Furthermore, in hyperplastic chest skin samples, miR-155 expression was lower than in normal chest skin (p = 0,026). These results suggest that miR-155 expression may modulate the microenvironmental susceptibility to cancer development and that high miR155 levels may be protective against the carcinogenesis induced by HPV16. PMID:25625305

  12. Effects of EGFR Inhibitor on Helicobacter pylori Induced Gastric Epithelial Pathology in Vivo

    Directory of Open Access Journals (Sweden)

    Philip A. Robinson

    2013-10-01

    Full Text Available Helicobacter pylori transactivates the Epidermal Growth Factor Receptor (EGFR and predisposes to gastric cancer development in humans and animal models. To examine the importance of EGFR signalling to gastric pathology, this study investigated whether treatment of Mongolian gerbils with a selective EGFR tyrosine kinase inhibitor, EKB-569, altered gastric pathology in chronic H. pylori infection. Gerbils were infected with H. pylori and six weeks later received either EKB-569-supplemented, or control diet, for 32 weeks prior to sacrifice. EKB-569-treated H. pylori-infected gerbils had no difference in H. pylori colonisation or inflammation scores compared to infected animals on control diet, but showed significantly less corpus atrophy, mucous metaplasia and submucosal glandular herniations along with markedly reduced antral and corpus epithelial proliferation to apoptosis ratios. EKB-569-treated infected gerbils had significantly decreased abundance of Cox-2, Adam17 and Egfr gastric transcripts relative to infected animals on control diet. EGFR inhibition by EKB-569 therefore reduced the severity of pre-neoplastic gastric pathology in chronically H. pylori-infected gerbils. EKB-569 increased gastric epithelial apoptosis in H. pylori-infected gerbils which counteracted some of the consequences of increased gastric epithelial cell proliferation. Similar chemopreventative strategies may be useful in humans who are at high risk of developing H.pylori-induced gastric adenocarcinoma.

  13. Expression of miR-146a, miR-155, and miR-223 in formalin-fixed paraffin-embedded synovial tissues of patients with rheumatoid arthritis and osteoarthritis.

    Science.gov (United States)

    Kriegsmann, Mark; Randau, Thomas M; Gravius, Sascha; Lisenko, Katharina; Altmann, Carolin; Arens, Norbert; Kriegsmann, Jörg

    2016-07-01

    Rheumatoid arthritis (RA) is a chronic autoimmune disease with a heterogeneous clinical presentation affecting about 1 % of adults in developed countries. Currently, the diagnosis is based on the revised criteria of the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) from 2010. These criteria include clinical and laboratory parameters. Because of the variability of the clinical picture, delayed diagnosis of RA occurs in a significant subset of patients. Therefore, the discovery of novel biomarkers that improve the diagnosis of RA is of particular interest. Recently, it became evident that miRNAs have regulatory activities in physiologic processes and human diseases. Upregulation of miR-146a, miR-155, and miR-223 has been shown in various compartments such as serum, blood, synovial fluid, and tissues in patients with RA. A total of 87 samples were analyzed (RA 50, osteoarthritis (OA) 37). RNA was isolated from formalin-fixed paraffin-embedded synovial tissue (FFPE). The relative expression of miR-146a, miR-155, and miR-223 was determined by comparison to a housekeeping RNA molecule (snRNA U6) and an RNA pool from histologically and clinically verified OA samples. miR-146a, miR-155, and miR-223 were significantly elevated in RA compared to OA synovial tissues (p < 0.001). A strong correlation between the miRNAs could be observed. The sensitivity and specificity for the detection of RA were 0.76/0.80 (miR-146a), 0.80/0.95 (miR-155), and 0.86/0.81 (miR-223). The combination of miR-155 and miR-223 resulted in the highest area under the curve (AUC 0.92) with a sensitivity and specificity of 0.84/0.91, respectively. Significantly higher expression levels of miR-146a, miR-155, and miR-223 in FFPE synovial tissue samples of patients with established RA compared to patients with OA were shown. The usefulness of these miRs for the differential diagnosis of early phases of RA against OA remains to be investigated.

  14. CD44 plays a functional role in Helicobacter pylori-induced epithelial cell proliferation.

    Directory of Open Access Journals (Sweden)

    Nina Bertaux-Skeirik

    2015-02-01

    Full Text Available The cytotoxin-associated gene (Cag pathogenicity island is a strain-specific constituent of Helicobacter pylori (H. pylori that augments cancer risk. CagA translocates into the cytoplasm where it stimulates cell signaling through the interaction with tyrosine kinase c-Met receptor, leading cellular proliferation. Identified as a potential gastric stem cell marker, cluster-of-differentiation (CD CD44 also acts as a co-receptor for c-Met, but whether it plays a functional role in H. pylori-induced epithelial proliferation is unknown. We tested the hypothesis that CD44 plays a functional role in H. pylori-induced epithelial cell proliferation. To assay changes in gastric epithelial cell proliferation in relation to the direct interaction with H. pylori, human- and mouse-derived gastric organoids were infected with the G27 H. pylori strain or a mutant G27 strain bearing cagA deletion (∆CagA::cat. Epithelial proliferation was quantified by EdU immunostaining. Phosphorylation of c-Met was analyzed by immunoprecipitation followed by Western blot analysis for expression of CD44 and CagA. H. pylori infection of both mouse- and human-derived gastric organoids induced epithelial proliferation that correlated with c-Met phosphorylation. CagA and CD44 co-immunoprecipitated with phosphorylated c-Met. The formation of this complex did not occur in organoids infected with ∆CagA::cat. Epithelial proliferation in response to H. pylori infection was lost in infected organoids derived from CD44-deficient mouse stomachs. Human-derived fundic gastric organoids exhibited an induction in proliferation when infected with H. pylori that was not seen in organoids pre-treated with a peptide inhibitor specific to CD44. In the well-established Mongolian gerbil model of gastric cancer, animals treated with CD44 peptide inhibitor Pep1, resulted in the inhibition of H. pylori-induced proliferation and associated atrophic gastritis. The current study reports a unique

  15. Effect of Di(2-ethylhexylphthalate on Helicobacter pylori-Induced Apoptosis in AGS Cells

    Directory of Open Access Journals (Sweden)

    Chuang-Hao Lin

    2013-01-01

    Full Text Available Plastic products are wildly used in human life. Di(2-ethylhexylphthalate (DEHP is an essential additive in plastic manufacturing and is used as plasticizer for many products including plastic food packaging. DEHP is a teratogenic compound and can cause potent reproductive toxicity. DEHP can also cause liver damage, peroxisome proliferation, and carcinogenesis. DEHP is also strongly associated with peptic ulcers and gastric cancer; however, the underlying effect and mechanism of DEHP on the gastrointestinal tract are not entirely clear. The oral infection route of H. pylori parallels the major ingestion route of DEHP into the human body. Therefore, we wanted to study the effect of DEHP and H. pylori exposure on the human gastric epithelial cell line, AGS (gastric adenocarcinoma. The viability of the AGS cell line was significantly lower in 80 μM-DEHP and H. pylori (MOI = 100 : 1 coexposure than DEHP or H. pylori alone. DEHP and H. pylori coexposure also induced caspase-3 activation, and increased Bax/Bcl-2 ratio and DNA fragmentation in AGS cells. These results indicate that DEHP can enhance H. pylori cytotoxicity and induce gastric epithelial cell apoptosis. Therefore, it is possible that DEHP and H. pylori coexposure might enhance the disruption of the gastric mucosa integrity and potentially promote the pathogenesis of gastric carcinogenesis.

  16. Unexpected positive control of NFκB and miR-155 by DGKα and ζ ensures effector and memory CD8+ T cell differentiation

    Science.gov (United States)

    Yang, Jialong; Zhang, Ping; Krishna, Sruti; Wang, Jinli; Lin, Xingguang; Huang, Hongxiang; Xie, Danli; Gorentla, Balachandra; Huang, Rick; Gao, Jimin; Li, Qi-Jing; Zhong, Xiao-Ping

    2016-01-01

    Signals from the T-cell receptor (TCR) and γ-chain cytokine receptors play crucial roles in initiating activation and effector/memory differentiation of CD8 T-cells. We report here that simultaneous deletion of both diacylglycerol kinase (DGK) α and ζ (DKO) severely impaired expansion of CD8 effector T cells and formation of memory CD8 T-cells after Listeria monocytogenes infection. Moreover, ablation of both DGKα and ζ in preformed memory CD8 T-cells triggered death and impaired homeostatic proliferation of these cells. DKO CD8 T-cells were impaired in priming due to decreased expression of chemokine receptors and migration to the draining lymph nodes. Moreover, DKO CD8 T-cells were unexpectedly defective in NFκB-mediated miR-155 transcript, leading to excessive SOCS1 expression and impaired γ-chain cytokine signaling. Our data identified a DGK-NFκB-miR-155-SOCS1 axis that bridges TCR and γ-chain cytokine signaling for robust CD8 T-cell primary and memory responses to bacterial infection. PMID:27014906

  17. Transfection of Kasumi-1 cells with a new type of polymer carriers loaded with miR-155 and antago-miR-155.

    Science.gov (United States)

    Klimenko, O V; Shtilman, M I

    2013-04-01

    Previous studies have demonstrated functional roles for microRNAs (miRNAs) in various aspects of normal and malignant hematopoiesis, including lineage commitment, differentiation, apoptosis and maturation. In vivo delivery of naked DNA, oligonucleotides and miRNAs is complicated by their low stability, rapid degradation and inefficient delivery into target cells. In our experiments, we used a new type of polymer carriers to monitor the effects of miR-155 and antago-miR-155 on the morphology and genetics of Kasumi-1 cells. We obtained platelet-like cells from leukemic cells, and detected the expression of platelet marker genes after transfection with antago-miR-155. Our findings suggest that administration of miR mimics or antago-miRs as therapeutic agents is a desirable goal for future treatment of hematologic malignancies and that polymer-based carriers for the delivery of miR mimics or antago-miRs may provide a solution to the challenges of standard miR delivery approaches.

  18. High Dietary Salt Intake Exacerbates Helicobacter pylori-Induced Gastric Carcinogenesis

    OpenAIRE

    Gaddy, Jennifer A.; Radin, Jana N.; Loh, John T.; Zhang, Feng; Washington, M. Kay; Peek, Richard M.; Algood, Holly M. Scott; Cover, Timothy L.

    2013-01-01

    Persistent colonization of the human stomach with Helicobacter pylori is a risk factor for gastric adenocarcinoma, and H. pylori-induced carcinogenesis is dependent on the actions of a bacterial oncoprotein known as CagA. Epidemiological studies have shown that high dietary salt intake is also a risk factor for gastric cancer. To investigate the effects of a high-salt diet, we infected Mongolian gerbils with a wild-type (WT) cagA+ H. pylori strain or an isogenic cagA mutant strain and main...

  19. Role of miR-155 in invasion and metastasis of lung adenocarcinoma A549 cells%miR-155在肺腺癌 A549细胞侵袭和转移中的作用

    Institute of Scientific and Technical Information of China (English)

    程田力; 胡成平; 李敏; 顾其华; 安健

    2016-01-01

    目的:探讨 miR-155在肺腺癌侵袭和转移中的作用。方法采用实时荧光定量 PCR和原位杂交检测 miR-155在肺腺癌和癌旁组织以及转移淋巴结中的表达,采用划痕实验和 Transwell迁移实验检测 miR-155对 A549细胞的迁移和侵袭能力的影响;利用生物信息学软件预测 miR-155的靶基因,并采用双荧光素酶检测靶基因;采用 Western blot 和实时荧光定量 PCR 检测 miR-155调控靶基因鼠抗人第10号染色体同源缺失性磷酸酶张力蛋白(PTEN)的表达水平。结果实时荧光定量PCR 检测显示,肺腺癌组织、癌旁正常组织和转移淋巴结中的 miR-155表达水平分别为9.6±3.1、4.1±0.5和7.8±2.2。原位杂交检测显示,肺腺癌组织、癌旁正常组织和转移淋巴结中 miR-155阳性表达率分别为(75.4±20.2)%、(23.2±15.3)%和(60.4±25.1)%。划痕实验检测显示,miR-155模拟物组、miR-155模拟物对照组、miR-155抑制剂组和 miR-155抑制剂对照组24 h 伤口愈合率分别为(43.2±2.2)%、(21.3±4.2)%、(24.3±5.3)%和(35.2±5.1)%,而48 h 伤口愈合率分别为(75.2±4.5)%、(52.6±5.2)%、(39.4±4.2)%和(51.5±4.3)%。双荧光素酶报告基因检测显示,miR-155模拟物组与含有PTEN 3′UTR 野生型和突变型质粒共转染的荧光素酶值分别为4.7±0.5和7.3±0.7,而 miR-155模拟物对照组与含有 PTEN 3′UTR 野生型和突变型质粒共转染的荧光素酶值分别为7.8±0.9和7.5±0.8。实时荧光定量 PCR 检测显示,miR-155模拟物组、miR-155模拟物对照组、miR-155抑制剂组和 miR-155抑制剂对照组的 PTEN mRNA 相对表达水平分别为0.5±0.3、1.0±0.1、2.2±0.2和1.2±0.1。 Western blot 检测显示,miR-155模拟物组、miR-155模拟物对照组、miR-155抑制剂组和 miR-155抑制剂对照组的 PTEN 蛋白相对表达水平分别为0.4±0.1、1.0±0.3、2.8±0.2和1.4±0.1。 miR-155模拟物组与miR-155模拟物对照组、miR-155抑制剂组与 miR-155抑制剂对照组的 PTEN mRNA 和蛋白表达差异均有统计学意义(均 P<0.05)。结论miR-155可能是通过下调靶基因 PTEN 的表达而促进肺腺癌的侵袭和转移。%Objective To investigate the role and mechanism of miR-155 in invasion and metastasis of lung adenocarcinoma A549 cells.Methods Real-time PCR and fluorescence in situ hybridization were used to detect the miR-155 expression in patients′lung adenocarcinoma and adjacent tissue and lymph nodes.Scratch test and Transwell migration assay were used to assess the effect of miR-155 on the A549 cell migration and invasion capability.Bioinformatics software was used to predict the target genes of miR-155, and using luciferase to assay the target gene.Western blot and real-time PCR were performed to confirm the role of miR-155 expression in the regulation of target gene PTEN.Results The real-time quantitative PCR showed that the miR-155 expression levels in adjacent normal tissue, lung adenocarcinoma and metastatic lymph nodes were 4.1±0.5, 9.6±3.1 and 7.8±2.2, respectively.The in situ hybridization showed that the expression rates of miR-155 in the adjacent normal tissue, lung adenocarcinoma and metastatic lymph nodes were (23.2±15.3)%, (75.4±20.2 )% and (60.4±25.1)%,respectively.The Scratch assay showed that the wound healing rates in the miR-155 mimics group, miR-155 mimics NC group, miR-155 inhibitor group and miR-155 inhibitor NC group at 24 h were (43.2±2.2)%, (21.3±4.2)%, (24.3±5.3)%, and (35.2± 5.1)%, and that at 48 h were (75.2±4.5)%, (52.6±5.2)%, (39.4±4.2)%, and( 51.5±4.3)%, respectively.Dual luciferase reporter gene assay showed that the value of the luciferase in the miR -155 mimics group co-transfected with PTEN 3′UTR-containing wild-type and mutant plasmids were 4.7±0.5 and 7.3±0.7, and the miR-155 mimics luciferase values of the control group co-transfected with PTEN 3′UTR-containing wild-type and mutant plasmids were 7.8±0.9 and 7.5±0.8, respectively.The real-time quantitative fluorescence PCR showed that the relative expression of PTEN protein in the miR-155 mimics group, miR-155 mimics control group, miR-155 mimics inhibitor group, and miR-155 inhibitor control group were 0.5± 0.3, 1.0±0.1, 2.2±0.2 and 1.2 ±0.1, respectively.The Western blot assay detected that the relative expression of PTEN protein levels in the miR-155 mimics group, miR-155 mimics control group, miR-155 inhibitor group and miR-155 inhibitor control group were 0.4±0.1, 1.0±0.3, 2.8±0.2 and 1.4 ±0.1, respectively.The differences in PTEN mRNA and protein expressions of the four groups were statistically significant (P<0.05 for all).Conclusions miR-155 may promote the invasion and metastasis of lung adenocarcinoma through reducing the target PTEN gene expression.

  20. Early or late antibiotic intervention prevents Helicobacter pylori-induced gastric cancer in a mouse model.

    Science.gov (United States)

    Zhang, Songhua; Lee, Dong Soo; Morrissey, Rhiannon; Aponte-Pieras, Jose R; Rogers, Arlin B; Moss, Steven F

    2014-12-01

    H. pylori infection causes gastritis, peptic ulcers and gastric cancer. Eradicating H. pylori prevents ulcers, but to what extent this prevents cancer remains unknown, especially if given after intestinal metaplasia has developed. H. pylori infected wild-type (WT) mice do not develop cancer, but mice lacking the tumor suppressor p27 do so, thus providing an experimental model of H. pylori-induced cancer. We infected p27-deficient mice with H. pylori strain SS1 at 6-8 weeks of age. Persistently H. pylori-infected WT C57BL/6 mice served as controls. Mice in the eradication arms received antimicrobial therapy (omeprazole, metronidazole and clarithromycin) either "early" (at 15 weeks post infection, WPI) or "late" at 45 WPI. At 70 WPI, mice were euthanized for H. pylori determination, histopathology and cytokine/chemokine expression. Persistently infected mice developed premalignant lesions including high-grade dysplasia, whereas those given antibiotics did not. Histologic activity scores in the eradication groups were similar to each other, and were significantly decreased compared with controls for inflammation, epithelial defects, hyperplasia, metaplasia, atrophy and dysplasia. IP-10 and MIG levels in groups that received antibiotics were significantly lower than controls. There were no significant differences in expression of IFN-γ, TNF-α, IL-1β, RANTES, MCP-1, MIP-1α or MIP-1β among the three groups. Thus, H. pylori eradication given either early or late after infection significantly attenuated gastric inflammation, gastric atrophy, hyperplasia, and dysplasia in the p27-deficient mice model of H. pylori-induced gastric cancer, irrespective of the timing of antibiotic administration. This was associated with reduced expression of IP-10 and MIG.

  1. Curcumin Inhibits Gastric Inflammation Induced by Helicobacter Pylori Infection in a Mouse Model

    Directory of Open Access Journals (Sweden)

    António M. Santos

    2015-01-01

    Full Text Available Helicobacter pylori (H. pylori infection triggers a sequence of gastric alterations starting with an inflammation of the gastric mucosa that, in some cases, evolves to gastric cancer. Efficient vaccination has not been achieved, thus it is essential to find alternative therapies, particularly in the nutritional field. The current study evaluated whether curcumin could attenuate inflammation of the gastric mucosa due to H. pylori infection. Twenty-eight C57BL/6 mice, were inoculated with the H. pylori SS1 strain; ten non-infected mice were used as controls. H. pylori infection in live mice was followed-up using a modified 13C-Urea Breath Test (13C-UBT and quantitative real-time polymerase chain reaction (PCR. Histologically confirmed, gastritis was observed in 42% of infected non-treated mice at both 6 and 18 weeks post-infection. These mice showed an up-regulation of the expression of inflammatory cytokines and chemokines, as well as of toll-like receptors (TLRs and MyD88, at both time points. Treatment with curcumin decreased the expression of all these mediators. No inflammation was observed by histology in this group. Curcumin treatment exerted a significant anti-inflammatory effect in H. pylori-infected mucosa, pointing to the promising role of a nutritional approach in the prevention of H. pylori induced deleterious inflammation while the eradication or prevention of colonization by effective vaccine is not available.

  2. Helicobacter pylori-induced gastric pathology: insights from in vivo and ex vivo models

    Science.gov (United States)

    Williams, Jonathan M.

    2017-01-01

    ABSTRACT Gastric colonization with Helicobacter pylori induces diverse human pathological conditions, including superficial gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma and its precursors. The treatment of these conditions often relies on the eradication of H. pylori, an intervention that is increasingly difficult to achieve and that does not prevent disease progression in some contexts. There is, therefore, a pressing need to develop new experimental models of H. pylori-associated gastric pathology to support novel drug development in this field. Here, we review the current status of in vivo and ex vivo models of gastric H. pylori colonization, and of Helicobacter-induced gastric pathology, focusing on models of gastric pathology induced by H. pylori, Helicobacter felis and Helicobacter suis in rodents and large animals. We also discuss the more recent development of gastric organoid cultures from murine and human gastric tissue, as well as from human pluripotent stem cells, and the outcomes of H. pylori infection in these systems. PMID:28151409

  3. Stress-induced hemorrhagic gastric ulcer after successful Helicobacter pylori eradication: two case reports

    Directory of Open Access Journals (Sweden)

    Miyamoto Mitsuaki

    2011-06-01

    Full Text Available Abstract Introduction Helicobacter pylori infection is a major cause of gastric ulcers, and Helicobacter pylori eradication drastically reduces ulcer recurrence. It has been reported, however, that severe physical stress is closely associated with gastric ulceration even in Helicobacter pylori -negative patients. Case presentation We report the cases of a 47-year-old Japanese man and a 69-year-old Japanese man who developed psychological stress-induced hemorrhagic gastric ulcers, in both of whom Helicobacter pylori had been successfully eradicated. Conclusion Our cases strongly suggest that not only physical but also psychological stress is still an important pathogenic factor for peptic ulceration and accordingly that physicians should pay attention to the possible presence of psychological stress in the management of patients with peptic ulcers.

  4. Diet, microbial virulence, and Helicobacter pylori-induced gastric cancer.

    Science.gov (United States)

    Cover, Timothy L; Peek, Richard M

    2013-01-01

    Gastric adenocarcinoma is a leading cause of cancer-related death worldwide, and Helicobacter pylori infection is one of the strongest known risk factors for this malignancy. H. pylori strains exhibit a high level of genetic diversity, and the risk of gastric cancer is higher in persons carrying certain strain types (for example, those that contain a cag pathogenicity island or type s1 vacA alleles) than in persons carrying other strain types. Additional risk factors for gastric cancer include specific human genetic polymorphisms and specific dietary preferences (for example, a high-salt diet or a diet deficient in fruits and vegetables). Finally, iron-deficiency anemia is a risk factor for gastric cancer. Recent studies have provided evidence that several dietary risk factors for gastric cancer directly impact H. pylori virulence. In this review article, we discuss mechanisms by which diet can modulate H. pylori virulence and thereby influence gastric cancer risk.

  5. Diet, microbial virulence, and Helicobacter pylori-induced gastric cancer

    OpenAIRE

    Cover, Timothy L.; Peek, Jr, Richard M

    2013-01-01

    Gastric adenocarcinoma is a leading cause of cancer-related death worldwide, and Helicobacter pylori infection is one of the strongest known risk factors for this malignancy. H. pylori strains exhibit a high level of genetic diversity, and the risk of gastric cancer is higher in persons carrying certain strain types (for example, those that contain a cag pathogenicity island or type s1 vacA alleles) than in persons carrying other strain types. Additional risk factors for gastric cancer includ...

  6. Helicobacter pylori Antigens Inducing Early Immune Response in Infants.

    Science.gov (United States)

    Seo, Ji Hyun; Youn, Jong Hyuk; Kim, Eun A; Jun, Jin Su; Park, Ji Sook; Yeom, Jung Sook; Lim, Jae Young; Woo, Hyang Ok; Youn, Hee Shang; Ko, Gyung Hyuck; Park, Jin Sik; Baik, Seung Chul; Lee, Woo Kon; Cho, Myung Je; Rhee, Kwang Ho

    2017-07-01

    To identify the Helicobacter pylori antigens operating during early infection in sera from infected infants using proteomics and immunoblot analysis. Two-dimensional (2D) large and small gel electrophoresis was performed using H. pylori strain 51. We performed 2D immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) antibody immunoblotting using small gels on sera collected at the Gyeongsang National University Hospital from 4-11-month-old infants confirmed with H. pylori infection by pre-embedding immunoelectron microscopy. Immunoblot spots appearing to represent early infection markers in infant sera were compared to those of the large 2D gel for H. pylori strain 51. Corresponding spots were analyzed by matrix-assisted laser desorption/ionization time of flight-mass spectrometry (MALDI-TOF-MS). The peptide fingerprints obtained were searched in the National Center for Biotechnology Information (NCBI) database. Eight infant patients were confirmed with H. pylori infection based on urease tests, histopathologic examinations, and pre-embedding immunoelectron microscopy. One infant showed a 2D IgM immunoblot pattern that seemed to represent early infection. Immunoblot spots were compared with those from whole-cell extracts of H. pylori strain 51 and 18 spots were excised, digested in gel, and analyzed by MALDI-TOF-MS. Of the 10 peptide fingerprints obtained, the H. pylori proteins flagellin A (FlaA), urease β subunit (UreB), pyruvate ferredoxin oxidoreductase (POR), and translation elongation factor Ts (EF-Ts) were identified and appeared to be active during the early infection periods. These results might aid identification of serological markers for the serodiagnosis of early H. pylori infection in infants. © 2017 The Korean Academy of Medical Sciences.

  7. Lactic Acid Bacteria Strains Exert Immunostimulatory Effect on H. pylori-Induced Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Małgorzata Wiese

    2015-01-01

    Full Text Available The aim of this study was to find out if selected lactic acid bacteria (LAB strains (antagonistic or nonantagonistic against H. pylori in vitro would differ in their abilities to modulate the DCs maturation profiles reflected by their phenotype and cytokine expression patterns. Methods. Monocyte-derived DCs maturation was elicited by their direct exposure to the LAB strains of L. rhamnosus 900 or L. paracasei 915 (antagonistic and nonantagonistic to H. pylori, resp., in the presence or absence of H. pylori strain cagA+. The DCs maturation profile was assessed on the basis of surface markers expression and cytokines production. Results. We observed that the LAB strains and the mixtures of LAB with H. pylori are able to induce mature DCs. At the same time, the L. paracasei 915 leads to high IL-10/IL-12p70 cytokine ratio, in contrast to L. rhamnosus 900. Conclusions. This study showed that the analyzed lactobacilli strains are more potent stimulators of DC maturation than H. pylori. Interestingly from the two chosen LAB strains the antagonistic to H. pylori-L. rhamnosus strain 900 has more proinflammatory and probably antibactericidal properties.

  8. Involvement of Toll-like receptors on Helicobacter pylori-induced immunity.

    Directory of Open Access Journals (Sweden)

    Romy Käbisch

    Full Text Available Dendritic cells (DCs play a major role in the innate immune response since they recognize a broad repertoire of PAMPs mainly via Toll-like receptors (TLRs. During Helicobacter pylori (H. pylori infection, TLRs have been shown to be important to control cytokine response particularly in murine DCs. In the present study we analyzed the effect of blocking TLRs on human DCs. Co-incubation of human DCs with H. pylori resulted in the release of the pro-inflammatory cytokines IL-12p70, IL-6 and IL-10. Release of IL-12p70 and IL-10 was predominantly influenced when TLR4 signaling was blocked by adding specific antibodies, suggesting a strong influence on subsequent T cell responses through TLR4 activation on DCs. Co-incubation of H. pylori-primed DC with allogeneic CD4+ T cells resulted in the production of IFN-γ and IL-17A as well as the expression of Foxp3, validating a mixed Th1/Th17 and Treg response in vitro. Neutralization of TLR4 during H. pylori infection resulted in significantly decreased amounts of IL-17A and IFN-γ and reduced levels of Foxp3-expressing and IL-10-secreting T cells. Our findings suggest that DC cytokine secretion induced upon TLR4-mediated recognition of H. pylori influences inflammatory and regulatory T cell responses, which might facilitate the chronic bacterial persistence.

  9. Probiotics in Helicobacter pylori-induced peptic ulcer disease.

    Science.gov (United States)

    Boltin, Doron

    2016-02-01

    The ideal treatment regimen for the eradication Helicobacter pylori infection has yet to be identified. Probiotics, particularly Lactobacillus, Bifidobacterium and Saccharomyces, have been suggested as adjuncts to antibiotics for the treatment of H. pylori. There is in vitro evidence that probiotics dampen the Th1 response triggered by H. pylori, attenuate H. pylori associated hypochlorhydria and secrete bacteriocidal metabolites. Probiotics interact with the innate host immune system through adherence to the gastric epithelium and secretion of bacterial adhesins. In prospective human studies, probiotic monotherapy effectively decrease H. pylori density (expired (13)CO2) by 2.0%-64.0%. Probiotic monotherapy has also been shown to eradicate H. pylori in up to 32.5%, although subsequent recrudescence is likely. Eleven meta-analyses have evaluated the efficacy of probiotics as adjuvants to antibiotics for the eradication of H. pylori. The addition of a probiotic increased treatment efficacy, OR 1.12-2.07. This benefit is probably strain-specific and may only be significant with relatively ineffective antibiotic regimens. The pooled prevalence of adverse effects was 12.9%-31.5% among subjects receiving adjuvant probiotics, compared with 24.3%-45.9% among controls. Diarrhea in particular was significantly reduced in subjects receiving adjuvant probiotics, compared with controls (OR 0.16-0.47). A reduction in adverse events other than diarrhea is variable. Despite the apparent benefit on efficacy and side effects conferred by probiotics, the optimal probiotic species, dose and treatment duration has yet to be determined. Further studies are needed to identify the probiotic, antibiotic and patient factors which might predict benefit from probiotic supplementation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Inflammation-induced miRNA-155 inhibits self-renewal of neural stem cells via suppression of CCAAT/enhancer binding protein β (C/EBPβ) expression

    Science.gov (United States)

    Obora, Kayoko; Onodera, Yuta; Takehara, Toshiyuki; Frampton, John; Hasei, Joe; Ozaki, Toshifumi; Teramura, Takeshi; Fukuda, Kanji

    2017-01-01

    Intracerebral inflammation resulting from injury or disease is implicated in disruption of neural regeneration and may lead to irreversible neuronal dysfunction. Analysis of inflammation-related microRNA profiles in various tissues, including the brain, has identified miR-155 among the most prominent miRNAs linked to inflammation. Here, we hypothesize that miR-155 mediates inflammation-induced suppression of neural stem cell (NSC) self-renewal. Using primary mouse NSCs and human NSCs derived from induced pluripotent stem (iPS) cells, we demonstrate that three important genes involved in NSC self-renewal (Msi1, Hes1 and Bmi1) are suppressed by miR-155. We also demonstrate that suppression of self-renewal genes is mediated by the common transcription factor C/EBPβ, which is a direct target of miR-155. Our study describes an axis linking inflammation and miR-155 to expression of genes related to NSC self-renewal, suggesting that regulation of miR-155 may hold potential as a novel therapeutic strategy for treating neuroinflammatory diseases. PMID:28240738

  11. Lactobacillus acidophilus ameliorates H. pylori-induced gastric inflammation by inactivating the Smad7 and NFκB pathways

    Directory of Open Access Journals (Sweden)

    Yang Yao-Jong

    2012-03-01

    Full Text Available Abstract Background H. pylori infection may trigger Smad7 and NFκB expression in the stomach, whereas probiotics promote gastrointestinal health and improve intestinal inflammation caused by pathogens. This study examines if probiotics can improve H. pylori-induced gastric inflammation by inactivating the Smad7 and NFκB pathways. Results Challenge with H. pylori increased IL-8 and TNF-α expressions but not TGF-β1 in MKN45 cells. The RNA levels of Smad7 in AGS cells increased after H. pylori infection in a dose-dependent manner. A higher dose (MOI 100 of L. acidophilus pre-treatment attenuated the H. pylori-induced IL-8 expressions, but not TGF-β1. Such anti-inflammatory effect was mediated via increased cytoplasmic IκBα and depletion of nuclear NFκB. L. acidophilus also inhibited H. pylori-induced Smad7 transcription by inactivating the Jak1 and Stat1 pathways, which might activate the TGF-β1/Smad pathway. L. acidophilus pre-treatment ameliorated IFN-γ-induced Smad7 translation level and subsequently reduced nuclear NF-κB production, as detected by western blotting. Conclusions H. pylori infection induces Smad7, NFκB, IL-8, and TNF-α production in vitro. Higher doses of L. acidophilus pre-treatment reduce H. pylori-induced inflammation through the inactivation of the Smad7 and NFκB pathways.

  12. Pathobiology of Helicobacter pylori-induced Gastric Cancer

    Science.gov (United States)

    Amieva, Manuel; Peek, Richard M.

    2015-01-01

    Colonization of the human stomach by Helicobacter pylori and its role in causing gastric cancer is one of the richest examples of complex relationship among human cells, microbes, and their environment. It is also a puzzle of enormous medical importance given the incidence and lethality of gastric cancer worldwide. We review recent findings that have changed how we view these relationships and affected the direction of gastric cancer research. For example, recent data indicate that subtle mismatches between host and microbe genetic traits greatly affect risk of gastric cancer. The ability of H pylori and its oncoprotein CagA to reprogram epithelial cells and activate properties of stemness demonstrates the sophisticated relationship among H pylori and progenitor cells in the gastric mucosa. The observation that cell-associated H pylori can colonize the gastric glands and directly affect precursor and stem cells supports these observations. The ability to mimic these interactions in human gastric organoid cultures as well as animal models will allow investigators to more fully unravel the extent of H pylori control on the renewing gastric epithelium. Finally, our realization that external environmental factors, such as dietary components and essential micronutrients, as well as the gastrointestinal microbiota, can change the balance between H pylori’s activity as a commensal or a pathogen has provided direction to studies aimed at defining the full carcinogenic potential of this organism. PMID:26385073

  13. Astaxanthin and β-carotene in Helicobacter pylori-induced Gastric Inflammation: A Mini-review on Action Mechanisms.

    Science.gov (United States)

    Kang, Hyunju; Kim, Hyeyoung

    2017-06-01

    Helicobacter pylori is a dominant bacterium living in the human gastric tissues. In H. pylori-infected tissues, the infiltrated inflammatory cells produce reactive oxygen species (ROS), leading to gastric inflammation with production of various mediators. According to numerous epidemiological studies, dietary carotenoids may prevent gastric inflammation due to their antioxidant properties. Recent studies showed that antioxidant and anti-inflammatory effects of astaxanthin and β-carotene may contribute to inhibition of H. pylori-induced gastric inflammation. Astaxanthin changes H. pylori-induced activation of T helper cell type 1 response towards T helper cell type 2 response in the infected tissues. Astaxanthin inhibits the growth of H. pylori. Even though astaxanthin reduces H. pylori-induced gastric inflammation, it does not reduce cytokine levels in the infected tissues. β-Carotene suppresses ROS-mediated inflammatory signaling, including mitogen-activated protein kinases and redox-sensitive transcription factors, and reduces expression of inflammatory mediators, including interleukin-8, inducible nitric oxide synthase, and cyclooxygenase-2 in the infected tissues. Therefore, consumption of astaxanthin- and β-carotene-rich foods may be beneficial to prevent H. pylori-induced gastric inflammation. This review will summarize anti-inflammatory mechanisms of astaxanthin and β-carotene in H. pylori-mediated gastric inflammation.

  14. Inhibitory effect of Raphanobrassica on Helicobacter pylori-induced gastritis in Mongolian gerbils.

    Science.gov (United States)

    Yamada, Takanori; Wei, Min; Toyoda, Takeshi; Yamano, Shoutaro; Wanibuchi, Hideki

    2014-08-01

    Helicobacter pylori (H. pylori) infection is well known to be associated with chronic gastritis and also development of gastric cancer. Raphanobrassica (RB) is an intergeneric hybrid of the genera Raphanus (radish) and Brassica (cabbages) containing appreciable amounts of glucoraphanin (GR) and glucoraphenin (GRe), which are actively hydrolyzed by the enzyme myrosinase to sulforaphane and sulforaphene, respectively. Both of these metabolites exert antimicrobial and anti-inflammatory activity. The purpose of the present study was to investigate the effect of two freeze-dried products of RB (RB1 and RB2) on H. pylori-induced gastritis in Mongolian gerbils. Six-week-old male Mongolian gerbils were inoculated orally with H. pylori (ATCC 43504), and 2weeks later were fed diets containing no additives or diets supplemented with 2% RB1 (containing both GR and GRe) or 2% RB2 (containing GR only) for 10weeks. In the RB1, but not the RB2 group, mononuclear cell infiltration, mRNA expression of IL-6, and cell proliferation in the gastric mucosa were significantly suppressed. These results indicate that RB1 containing both GR and GRe exerted significant inhibitory effects on H. pylori-induced gastritis in Mongolian gerbils apparently mediated via suppression of IL-6 expression and chronic inflammation.

  15. Detouring the Undesired Route of Helicobacter pylori-Induced Gastric Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Ki Baik Hahm

    2011-07-01

    Full Text Available Epidemiological and experimental evidence has emerged that a dysregulated inflammation is associated with most of the tumors, and many studies have begun to unravel the molecular pathways linking inflammation and cancer. As a typical example linking these associations, Helicobacter pylori (H. pylori infection-associated atrophic gastritis has been recognized as precursor lesion of gastric cancer. The identification of transcription factors such as NF-κB and STAT3, and their gene products such as IL-8, COX-2, iNOS, cytokines, chemokines and their receptors, etc have laid the molecular foundation for our understanding of the decisive role of inflammation in carcinogenesis. In addition to the role as the initiator of cancer, inflammation contributes to survival and proliferation of malignant cells, tumor angiogenesis, and even metastasis. In this review, the fundamental mechanisms of H. pylori-induced carcinogenesis as well as the possibility of cancer prevention through suppressing H. pylori-induced inflammation are introduced. We infer that targeting inflammatory pathways have a potential role to detour the unpleasant journey to H. pylori-associated gastric carcinogenesis.

  16. Detouring the Undesired Route of Helicobacter pylori-Induced Gastric Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun-Hee; Hong, Kyung-Sook; Hong, Hua [Lab of Translational Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, 7-45 Songdo-dong, Yeonsu-gu, Incheon 406-840 (Korea, Republic of); Hahm, Ki Baik, E-mail: hahmkb@gachon.ac.kr [Lab of Translational Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, 7-45 Songdo-dong, Yeonsu-gu, Incheon 406-840 (Korea, Republic of); Department of Gastroenterology, Gachon Graduate School of Medicine, Gil Hospital, Incheon 406-840 (Korea, Republic of)

    2011-07-25

    Epidemiological and experimental evidence has emerged that a dysregulated inflammation is associated with most of the tumors, and many studies have begun to unravel the molecular pathways linking inflammation and cancer. As a typical example linking these associations, Helicobacter pylori (H. pylori) infection-associated atrophic gastritis has been recognized as precursor lesion of gastric cancer. The identification of transcription factors such as NF-κB and STAT3, and their gene products such as IL-8, COX-2, iNOS, cytokines, chemokines and their receptors, etc have laid the molecular foundation for our understanding of the decisive role of inflammation in carcinogenesis. In addition to the role as the initiator of cancer, inflammation contributes to survival and proliferation of malignant cells, tumor angiogenesis, and even metastasis. In this review, the fundamental mechanisms of H. pylori-induced carcinogenesis as well as the possibility of cancer prevention through suppressing H. pylori-induced inflammation are introduced. We infer that targeting inflammatory pathways have a potential role to detour the unpleasant journey to H. pylori-associated gastric carcinogenesis.

  17. Helicobacter pylori Might Induce TGF-β1-Mediated EMT by Means of cagE.

    Science.gov (United States)

    Chang, Hyun; Kim, Nayoung; Park, Ji Hyun; Nam, Ryoung Hee; Choi, Yoon Jeong; Park, Seon Mee; Choi, Yoon Jin; Yoon, Hyuk; Shin, Cheol Min; Lee, Dong Ho

    2015-12-01

    Epithelial-mesenchymal transition (EMT), in which polarized epithelial cells have mesenchymal cell phenotypes, is thought to be a key process of invasion and metastasis of cancer. Transforming growth factor beta-1 (TGF-β1) is known to be carcinogenic and Helicobacter pylori is a predominant carcinogen of gastric cancer. Our study aimed to determine whether TGF-β1 or H. pylori infection enhances EMT process and cytotoxin-associated gene E (CagE) is associated with EMT. Human gastric cancer cell AGS and MKN45 were treated with recombinant TGF-β1 or H. pylori including cagE-negative (ΔcagE) mutant. Besides the assessment of EMT-related markers expression levels by means of RT-qPCR, Western blot, and immunofluorescence assay, the induction of in vitro EMT on gastric cancer cells (AGS and MKN cell lines) was confirmed by wound-healing assay and invasion assay. When gastric cancer cells were treated with TGF-β1 or various strains of cagE-positive H. pylori, EMT-related marker altered significantly. However, the ΔcagE mutant did not. Wound-healing assay and invasion assay showed enhanced migration ability of the cells treated with cagE-positive H. pylori but not in ΔcagE mutant. EMT induction in gastric cancer cells by TGF-β1 was confirmed. Only infection with cagE-positive H. pylori upregulated the TGF-β1-mediated EMT pathway and consequently promotes EMT. Therefore, H. pylori might induce TGF-β1-mediated EMT associated with the cagE. © 2015 John Wiley & Sons Ltd.

  18. Protective effect of Korean Red Ginseng extract against Helicobacter pylori-induced gastric inflammation in Mongolian gerbils

    Directory of Open Access Journals (Sweden)

    Minkyung Bae

    2014-01-01

    Full Text Available Helicobacter pylori-induced gastric inflammation includes induction of inflammatory mediators interleukin (IL-8 and inducible nitric oxide synthase (iNOS, which are mediated by oxidant-sensitive transcription factor NF-κB. High levels of lipid peroxide (LPO and increased activity of myeloperoxidase (MPO, a biomarker of neutrophil infiltration, are observed in H. pylori-infected gastric mucosa. Panax ginseng Meyer, a Korean herb medicine, is widely used in Asian countries for its biological activities including anti-inflammatory efficacy. The present study aims to investigate whether Korean Red Ginseng extract (RGE inhibits H. pylori-induced gastric inflammation in Mongolian gerbils. One wk after intragastric inoculation with H. pylori, Mongolian gerbils were fed with either the control diet or the diet containing RGE (200 mg RGE/gerbil for 6 wk. The following were determined in gastric mucosa: the number of viable H. pylori in stomach; MPO activity; LPO level; mRNA and protein levels of keratinocyte chemoattractant factor (KC, a rodent IL-8 homolog, IL-1β, and iNOS; protein level of phospho-IκBα (which reflects the activation of NF-κB; and histology. As a result, RGE suppressed H. pylori-induced mRNA and protein levels of KC, IL-1β, and iNOS in gastric mucosa. RGE also inhibited H. pylori-induced phosphorylation of IκBα and increases in LPO level and MPO activity of gastric mucosa. RGE did not affect viable H. pylori colonization in the stomach, but improved the histological grade of infiltration of polymorphonuclear neutrophils, intestinal metaplasia, and hyperplasia. In conclusion, RGE inhibits H. pylori-induced gastric inflammation by suppressing induction of inflammatory mediators (KC, IL-1β, iNOS, MPO activity, and LPO level in H. pylori-infected gastric mucosa.

  19. Cutting Edge: Helicobacter pylori Induces Nuclear Hypersegmentation and Subtype Differentiation of Human Neutrophils In Vitro

    Science.gov (United States)

    Whitmore, Laura C.; Weems, Megan N.

    2017-01-01

    Helicobacter pylori infects the human stomach and causes a spectrum of disease that includes gastritis, peptic ulcers, and gastric adenocarcinoma. A chronic, neutrophil-rich inflammatory response characterizes this infection. It is established that H. pylori stimulates neutrophil chemotaxis and a robust respiratory burst, but other aspects of this interaction are incompletely defined. We demonstrate here that H. pylori induces N1-like subtype differentiation of human neutrophils as indicated by profound nuclear hypersegmentation, a CD62Ldim, CD16bright, CD11bbright, CD66bbright, CD63bright surface phenotype, proinflammatory cytokine secretion, and cytotoxicity. Hypersegmentation requires direct neutrophil–H. pylori contact as well as transcription and both host and bacterial protein synthesis, but not urease, NapA, VacA, CagA, or CagT. The concept of neutrophil plasticity is new and, to our knowledge, these data are the first evidence that neutrophils can undergo subtype differentiation in vitro in response to bacterial pathogen infection. We hypothesize that these changes favor H. pylori persistence and disease. PMID:28148734

  20. Effect of Byrsonima crassa and Phenolic Constituents on Helicobacter pylori-Induced Neutrophils Oxidative Burst

    Directory of Open Access Journals (Sweden)

    Wagner Vilegas

    2011-12-01

    Full Text Available Byrsonima crassa Niedenzu (Malpighiaceae is used in Brazilian folk medicine for the treatment of diseases related mainly to gastric ulcers. In a previous study, our group described the gastric protective effect of the methanolic extract from the leaves of B. crassa. The present study was carried out to investigate the effects of methanolic extract and its phenolic compounds on the respiratory burst of neutrophils stimulated by H. pylori using a luminol-based chemiluminescence assay as well as their anti-H. pylori activity. The suppressive activity on oxidative burst of H. pylori-stimulated neutrophils was in the order of methyl gallate > (+-catechin > methanol extract > quercetin 3-O-α-l-arabinopyranoside > quercetin 3-O-β-d-galactopyranoside > amentoflavone. Methyl gallate, compound that induced the highest suppressive activity with IC50 value of 3.4 µg/mL, did not show anti-H. pylori activity. B. crassa could be considered as a potential source of natural antioxidant in gastric ulcers by attenuating the effects on the damage to gastric mucosa caused by neutrophil generated reactive oxygen species, even when H. pylori displays its evasion mechanisms.

  1. Regulation of tumour necrosis factor (TNF) induced apoptosis by soluble TNF receptors in Helicobacter pylori infection

    OpenAIRE

    Shibata, J; Goto, H.; Arisawa, T.; Niwa, Y.; Hayakawa, T.; Nakayama, A.; Mori, N.

    1999-01-01

    BACKGROUND—Tumour necrosis factor (TNF) is a predominant cytokine produced in the gastric mucosa of patients with Helicobacter pylori infection. TNF induces apoptosis in a variety of cells. The soluble TNF receptors (sTNF-Rs) can be divided into sTNF-RI and sTNF-RII, both of which inhibit TNF activity. However, their precise mechanisms remain unclear.
AIM—To investigate the role of sTNF-Rs in H pylori infection.
METHODS—In 40 patients, production of TNF and sTNF-Rs in gastric mucosa was measu...

  2. Rebamipide, a novel antiulcer agent, attenuates Helicobacter pylori induced gastric mucosal cell injury associated with neutrophil derived oxidants.

    Science.gov (United States)

    Suzuki, M; Miura, S; Mori, M; Kai, A; Suzuki, H; Fukumura, D; Suematsu, M; Tsuchiya, M

    1994-01-01

    The effect of rebamipide, a novel antiulcer compound, on Helicobacter pylori activated neutrophil dependent in vitro gastric epithelial cell injury was investigated. Luminol dependent chemiluminescence (ChL), which detects toxic oxidants from neutrophils exhibited a 12-fold increase when the bacterial suspension of H pylori was added to the isolated human neutrophils. This change was significantly attenuated by rebamipide at a concentration less than 1 mM, showing that rebamipide may inhibit oxidant production from H pylori elicited neutrophils. To assess whether rebamipide attenuates gastric mucosal injury, we tested its inhibitory action on H pylori induced gastric mucosal damage associated with neutrophils in vitro. Rabbit gastric mucosal cells were monolayered in culture wells and coincubated with human neutrophils and H pylori, and the cytotoxicity index was then calculated. Cultured gastric cells were significantly damaged when they were incubated with human neutrophils activated by H pylori. This cellular damage was attenuated by rebamipide in a dose-dependent manner. Furthermore, spectrophotometrical measurement showed that rebamipide (1 mM) inhibits urease activity by 21.7%. As monochloramine (an oxidant yielded by reaction of neutrophil derived chlorinated oxidant and ammonia) is proposed as an important toxic molecule in this model, the current findings suggest that the preventive effect of rebamipide on H pylori elicited neutrophil induced gastric mucosal injury may result from its inhibitory actions on the neutrophilic oxidative burst as well as H pylori derived urease activity. PMID:7959190

  3. Role of caspase-3/E-cadherin in helicobacter pylori-induced apoptosis of gastric epithelial cells.

    Science.gov (United States)

    Yang, Yongmei; Du, Jie; Liu, Fen; Wang, Xiaoyan; Li, Xiaohui; Li, Yuanjian

    2017-08-29

    This study was designed to investigate the role of caspase-3/E-cadherin in Helicobacter pylori (H. pylori) -induced gastric epithelial apoptosis in cells, animal models and clinical gastritis patients. In cultured gastric mucosal epithelial cells, gastric glandular epithelial cells and C57BL/6 mice, H. pylori infection significantly induced apoptosis of gastric epithelial cells, down-regulated full-length E-cadherin and Bcl-2 expression, and up-regulated cleaved-caspase-3, E-cadherin/carboxy-terminal fragment 3 and Bax expression. Z-DEVD-FMK, an inhibitor of caspase-3, attenuated the effect of H. pylori. E-cadherin overexpression significantly inhibited the apoptosis of GES-1 and SGC-7901 cells induced by the H. pylori. The results from clinical studies also showed down-regulation of E-cadherin, up-regulation of cleaved-caspase-3 expression and increased apoptosis in gastric tissues from gastritis patients with H. pylori infection. These results suggest that the caspase-3/E-cadherin pathway is involved in the apoptosis of gastric epithelial cells induced by H. pylori.

  4. How host regulation of Helicobacter pylori-induced gastritis protects against peptic ulcer disease and gastric cancer.

    Science.gov (United States)

    Dhar, Poshmaal; Ng, Garrett Z; Sutton, Philip

    2016-09-01

    The bacterial pathogen Helicobacter pylori is the etiological agent of a range of gastrointestinal pathologies including peptic ulcer disease and the major killer, gastric adenocarcinoma. Infection with this bacterium induces a chronic inflammatory response in the gastric mucosa (gastritis). It is this gastritis that, over decades, eventually drives the development of H. pylori-associated disease in some individuals. The majority of studies investigating H. pylori pathogenesis have focused on factors that promote disease development in infected individuals. However, an estimated 85% of those infected with H. pylori remain completely asymptomatic, despite the presence of pathogenic bacteria that drive a chronic gastritis that lasts many decades. This indicates the presence of highly effective regulatory processes in the host that, in most cases, keeps a check on inflammation and protect against disease. In this minireview we discuss such known host factors and how they prevent the development of H. pylori-associated pathologies.

  5. Synthesis and bioevaluation of novel 3,4,5-trimethoxybenzylbenzimidazole derivatives that inhibit Helicobacter pylori-induced pathogenesis in human gastric epithelial cells.

    Science.gov (United States)

    Chang, Chih-Shiang; Liu, Ju-Fang; Lin, Hwai-Jeng; Lin, Chia-Der; Tang, Chih-Hsin; Lu, Dah-Yuu; Sing, Yu-Ting; Chen, Li-Yu; Kao, Min-Chuan; Kuo, Sheng-Chu; Lai, Chih-Ho

    2012-02-01

    Helicobacter pylori infection is associated with gastritis, peptic ulcer, and even gastric malignancy. H. pylori's antibiotic resistance is the major obstacle preventing its eradication. A series of 3,4,5-trimethoxybenzylbenzimidazole derivatives were synthesized and evaluated for their anti-H. pylori activity. The compound, 2-fluorophenyl-5-methyl-1-(3,4,5-trimethoxybenzyl)benzimidazole (FMTMB), was determined as the most potent in the inhibition of H. pylori growth and pathogenesis of host cells. An in vitro H. pylori infection model revealed that FMTMB inhibited H. pylori adhesion and invasion of gastric epithelial cells. Results from this study provide evidence that FMTMB is a potent therapeutic agent that exhibits both anti-H. pylori growth properties and anti-H. pylori-induced pathogenesis of cells.

  6. Anti-Inflammatory Effects of Capsaicin and Piperine on Helicobacter pylori-Induced Chronic Gastritis in Mongolian Gerbils.

    Science.gov (United States)

    Toyoda, Takeshi; Shi, Liang; Takasu, Shinji; Cho, Young-Man; Kiriyama, Yuka; Nishikawa, Akiyoshi; Ogawa, Kumiko; Tatematsu, Masae; Tsukamoto, Tetsuya

    2016-04-01

    Spices have been used for thousands of years, and recent studies suggest that certain spices confer beneficial effects on gastric disorders. The purpose of this study was to evaluate possible chemopreventive effects of spice-derived compounds on Helicobacter pylori (H. pylori)-induced gastritis. We examined the inhibitory effects of curcumin, capsaicin, and piperine on H. pylori in vitro by determining the colony-forming units and real-time RT-PCR in H. pylori stimulated AGS gastric cancer cells. For in vivo analysis, 6-week-old SPF male Mongolian gerbils were infected with H. pylori, fed diets containing 5000 ppm curcumin, 100 ppm capsaicin, or 100 ppm piperine, and sacrificed after 13 weeks. All three compounds inhibited in vitro proliferation of H. pylori, with curcumin being the most effective. Infiltration of neutrophils and mononuclear cells was suppressed by piperine both in the antrum and corpus of H. pylori-infected gerbils. Capsaicin also decreased neutrophils in the antrum and corpus and mononuclear cell infiltration and heterotopic proliferative glands in the corpus. mRNA expression of Tnf-α and formation of phospho-IκB-α in the antrum were reduced by both capsaicin and piperine. In addition, piperine suppressed expression of Il-1β, Ifn-γ, Il-6, and iNos, while H. pylori UreA and other virulence factors were not significantly attenuated by any compounds. These results suggest that capsaicin and piperine have anti-inflammatory effects on H. pylori-induced gastritis in gerbils independent of direct antibacterial effects and may thus have potential for use in the chemoprevention of H. pylori-associated gastric carcinogenesis. © 2015 John Wiley & Sons Ltd.

  7. Analysis of T4SS-induced signaling by H. pylori using quantitative phosphoproteomics

    Directory of Open Access Journals (Sweden)

    Frithjof eGlowinski

    2014-07-01

    Full Text Available Helicobacter pylori is a Gram-negative bacterial pathogen colonizing the human stomach. Infection with H. pylori causes chronic inflammation of the gastric mucosa and may lead to peptic ulceration and/or gastric cancer. A major virulence determinant of H. pylori is the type IV secretion system (T4SS, which is used to inject the virulence factor CagA into the host cell, triggering a wide range of cellular signaling events. Here, we used a phosphoproteomic approach to investigate tyrosine signaling in response to host-pathogen interaction, using stable isotope labeling in cell culture (SILAC of AGS cells to obtain a differential picture between multiple infection conditions. Cells were infected with wild type H. pylori P12, a P12ΔCagA deletion mutant, and a P12ΔT4SS deletion mutant to compare signaling changes over time and in the absence of CagA or the T4SS. Tryptic peptides were enriched for tyrosine (Tyr phosphopeptides and analysed by nano-LC-Orbitrap MS. In total, 58 different phosphosites were found to be regulated following infection. The majority of phosphosites identified were kinases of the MAPK familiy. CagA and the T4SS were found to be key regulators of Tyr phosphosites. Our findings indicate that CagA primarily induces activation of ERK1 and integrin linked factors, whereas the T4SS primarily modulates JNK and p38 activation.

  8. Helicobacter pylori enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in human gastric epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Yi-Ying Wu; Hwei-Fang Tsai; We-Cheng Lin; Ai-Hsiang Chou; Hui-Ting Chen; Jyh-Chin Yang; Ping-I Hsu; Ping-Ning Hsu

    2004-01-01

    AIM: To investigate the relations between tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Helicobacter pylori(H pylori) infection in apoptosis of gastric epithelial cells and to assess the expression of TRAIL onthe surface of infiltrating T-cells in Hpylori-infected gastric mucosa.METHODS: Human gastric epithelial cell lines and primary gastric epithelial cells were co-cultured with H pylori in vitro, then recombinant TRAIL proteins were added to the culture. Apoptosis of gastric epithelial cells was determined by a specific ELISA for cell death. Infiltrating lymphocytes were isolated from H pylori-infected gastric mucosa, and expression of TRAIL in T cells was analyzed by flow cytometry.RESULTS: The apoptosis of gastric epithelial cell lines and primary human gastric epithelial cells was mildly increased by interaction with either TRAIL or H pylorialone. Interestingly,the apoptotic indices were markedly elevated when gastric epithelial cells were incubated with both TRAIL and H pylori (Control vsTRAIL and H pylori: 0.51±0.06 vs 2.29±0.27,P = 0.018). A soluble TRAIL receptor (DR4-Fc) could specifically block the TRAIL-mediated apoptosis. Further studies demonstrated that infiltrating T-cells in gastric mucosa expressed TRAIL on their surfaces, and the induction of TRAIL sensitivity by H pylori was dependent upon direct cell contact of viable bacteria, but not CagA and VacA of H pylori.CONCLUSION: H pylori can sensitize human gastric epithelial ceils and enhance susceptibility to TRAIL-mediated apoptosis. Modulation of host cell sensitivity to apoptosis by bacterial interaction adds a new dimension to the immunopathogenesis of H pylori infection.

  9. miR-155对含SH2区域的肌醇5’磷酸酶1转录后调控在急性髓系白血病发病机制中作用的初步研究%Preliminary study of role of post-transcription regulation on SH2 domain-containing inositol 5'-phosphatase 1 gene expression by miR-155 in the pathogenesis of acute myeloid leukemia

    Institute of Scientific and Technical Information of China (English)

    薛华; 赵松颖; 王静; 范丽霞; 化罗明; 罗建民

    2015-01-01

    目的 探讨miR-155对人类含SH2区域的肌醇5’磷酸酶1(SHIP1)的转录后调控在急性髓系白血病(AML)发病机制中的作用.方法 应用反转录聚合酶链反应(RT-PCR)法检测30例AML患者miR-155、SHIP1的mRNA表达水平,选取同年龄健康人骨髓为对照组.人白血病U937细胞转染miR-155类似物后,RT-PCR法检测转染细胞中miR-155、SHIP1的mRNA表达水平.Western blot法检测转染后细胞SHIP1、AKT、pAKT蛋白水平.流式细胞术检测转染后细胞凋亡的变化.结果 30例AML患者中,15例AML-M4及AML-M5患者SHIP1蛋白水平较非AML-M4及AML-M5患者明显降低,而miR-155表达水平相应升高(均P< 0.05).U937细胞转染miR-155后,SHIP1蛋白水平较转染阴性对照组降低(P<0.05),而p-AKT水平较转染阴性对照组明显升高,转染后细胞凋亡明显受抑(P<0.05).结论 miR-155可对SHIP1进行转录后调控,miR-155可能通过降低SHIP1活性而激活PI3K-AKT途径,抑制白血病细胞的凋亡,从而促进AML的发生.%Objective To investigate the role of microRNA-155 (miR-155) on post-transcription regulation of SH2 domain-containing inositol 5'-phosphatase 1 (SHIP1) gene expression in the pathogenesis of acute myeloid leukemia (AML).Methods Quantitative real-time polymerase chain reaction (RT-PCR) was performed to detect the expression of miR-155 and SHIP1 mRNA in the AML patients and controls.miR-155 mimics was transfected into U937cells (U937m) by using X-treme GENE siRNA transfection reagent.Cells without transfection (U937c) and cells with negative transfection (U937mc) were used as controls.RT-PCR was performed to detect the expression of miR-155 and SHIP1 mRNA in these cells.The expression of SHIP1,TAKT and pAKT were detected by Western blot in U937 cells.Apoptosis was studied by flow cytometry (FCM).Results The average level of SHIP1 protein content in 15 samples of patients with AML-M4 or AML-M5 from 30 AML patients was significantly lower compared with that of patients with the other types of AML,and the levels of miR-155 were significantly higher in the same group of patients (P < 0.05).Significantly decreased levels of SHIP1 protein were found in U937m cells compared that of U937c and U937mc (P < 0.05).Significantly decreased rate of apoptosis was observed in U937m cells compared with that of U937mc and U937c.U937m cells also exhibited no alteration in total AKT content,while increased p-AKT levels were found (P< 0.05).Conclusion SHIP1 was also a primary target of miR-155 in AML.Overexpression of miR-155 could activate PI3K-AKT pathway to depressing SHIP1 and decrease the apoptosis rate of AML cells.

  10. The gastrin receptor antagonist netazepide (YF476) prevents oxyntic mucosal inflammation induced by Helicobacter pylori infection in Mongolian gerbils.

    Science.gov (United States)

    Sørdal, Øystein; Waldum, Helge; Nordrum, Ivar S; Boyce, Malcolm; Bergh, Kåre; Munkvold, Bjørn; Qvigstad, Gunnar

    2013-12-01

    Long-term Helicobacter pylori infection causes gastritis leading to hypergastrinemia and predisposes to gastric cancer. Our aim was to assess the role of gastrin in oxyntic mucosal inflammation in H. pylori-infected Mongolian gerbils by means of the gastrin receptor antagonist netazepide (YF476). We studied 60 gerbils for 18 months and left five animals uninfected (control group), inoculated 55 with H. pylori, and treated 28 of the infected animals with netazepide (Hp+YF476 group). Twenty-seven infected animals were given no treatment (Hp group). We measured plasma gastrin and intraluminal pH. H. pylori detection and histologic evaluations of the stomach were carried out. All 55 inoculated animals were H. pylori positive at termination. Eighteen animals in the Hp group had gastritis. There was a threefold increase in mucosal thickness in the Hp group compared to the Hp+YF476 group, and a threefold increase in oxyntic neuroendocrine cells in the Hp group compared to the Hp+YF476 group (p pylori-induced gastritis in Mongolian gerbils. Thus, gastrin has a key role in the inflammatory reaction of the gastric mucosa to H. pylori infection in this species. © 2013 John Wiley & Sons Ltd.

  11. BiNGO及DAVID在miR-155靶基因富集分析中的应用%Application of BiNGO and DAVID in Biological Enrichment Analysis of miR-155 Target Genes

    Institute of Scientific and Technical Information of China (English)

    杨蓉; 蔡琳

    2012-01-01

    目的 通过对预测得到的miR-155靶基因进行生物信息学分析,探索和比较DAVID(Database for Annotation,Visualization and Integrated Discovery)及BiNGO(Biological Networks Gene Ontology tool)软件在基因本体(GO)及生物学通路富集分析中的应用,以期为miR-155靶基因的实验验证及生物学功能的研究提供理论指导.方法 利用TargetScan 6.0预测得到的miR-155靶基因作为分析的基因集合,通过BiNGO及DAVID对这个靶基因集合进行GO富集分析和生物通路富集分析,并对两个软件的富集分析结果进行比较和分析.结果 miR-155的预测靶基因集合分别富集在转录调控活性、蛋白激酶活性等分子功能上和代谢调控、转录调控、高分子生物合成、基因表达调控及信号转导等生物学过程中(P<0.01);进一步分析显示该基因集合在KEGG代谢通路数据库中,显著富集于T细胞受体信号通路、B细胞受体信号通路、MAPK信号通路、ErbB信号通路等7个信号通路和结直肠癌、急慢性髓性白血病等7个疾病通路中(P<0.05).结论 BiNGO和DAVID软件在miRNAs靶基因富集分析中各有优势,可以结合两个软件的分析结果对miRNAs靶基因集合进行生物学描述,为进一步的功能研究提供生物信息学指导.%Objective To explore and compare the DAVID (Database for Annotation, Visualization and Integrated Discovery) and BiNGO software for bioinformatics analysis through the Gene Ontology and biological pathway enrichment analysis of targets of miR-155,in order to provide theoretical guidance for experimental validation of miR-155 target genes and biological functions. Methods TargetScan 6. 0 algorithm was used to predict target genes of miR-155 , and the result as gene set was analyzed by DAVID and BiNGO software. The differences of enrichment analysis result between DAVID and BiNGO were compared. Results The gene set was mostly enriched in transcriptional regulation activity protein kinase activity(GO molecular function, P<0. 01) and metabolic regulation, transcriptional regulation, macromol-ecule biosynthesis, gene expression regulation,signal transduction(GO biological process, P<0. 01). In KEGG pathway, the gene set indicated an enrichment in T cell receptor signaling pathway, B cell receptor signaling pathway, MAPK signaling pathways, ErbB signaling pathway, etc(signal transduction pathway, P<0. 05) and colorectal cancer, acute and chronic myeloid leukemia (human diseases pathway,P<0. 05). Conclusion BiNGO and DAVID have their own advantages, the combination of two software analysis of miRNAs target gene sets for biological description can provide bioinformatics basis for further functional studies.

  12. Src homology 2 domain-containing inositol-5-phosphatase and CCAAT enhancer-binding protein beta are targeted by miR-155 in B cells of Emicro-MiR-155 transgenic mice

    DEFF Research Database (Denmark)

    Costinean, Stefan; Sandhu, Sukhinder K; Pedersen, Irene M

    2009-01-01

    We showed that Emicro-MiR-155 transgenic mice develop acute lymphoblastic leukemia/high-grade lymphoma. Most of these leukemias start at approximately 9 months irrespective of the mouse strain. They are preceded by a polyclonal pre-B-cell proliferation, have variable clinical presentation......, are transplantable, and develop oligo/monoclonal expansion. In this study, we show that in these transgenic mice the B-cell precursors have the highest MiR-155 transgene expression and are at the origin of the leukemias. We determine that Src homology 2 domain-containing inositol-5-phosphatase (SHIP) and CCAAT...... a chain of events that leads to the accumulation of large pre-B cells and acute lymphoblastic leukemia/high-grade lymphoma....

  13. Epidermal growth factor receptor inhibition downregulates Helicobacter pylori-induced epithelial inflammatory responses, DNA damage and gastric carcinogenesis.

    Science.gov (United States)

    Sierra, Johanna C; Asim, Mohammad; Verriere, Thomas G; Piazuelo, M Blanca; Suarez, Giovanni; Romero-Gallo, Judith; Delgado, Alberto G; Wroblewski, Lydia E; Barry, Daniel P; Peek, Richard M; Gobert, Alain P; Wilson, Keith T

    2017-05-04

    Gastric cancer is the third leading cause of cancer death worldwide and infection by Helicobacter pylori is the strongest risk factor. We have reported increased epidermal growth factor receptor (EGFR) phosphorylation in the H. pylori-induced human carcinogenesis cascade, and association with DNA damage. Our goal was to determine the role of EGFR activation in gastric carcinogenesis. We evaluated gefitinib, a specific EGFR inhibitor, in chemoprevention of H. pylori-induced gastric inflammation and cancer development. Mice with genetically targeted epithelial cell-specific deletion of Egfr (Efgr(Δepi) mice) were also used. In C57BL/6 mice, gefitinib decreased Cxcl1 and Cxcl2 expression by gastric epithelial cells, myeloperoxidase-positive inflammatory cells in the mucosa and epithelial DNA damage induced by H. pylori infection. Similar reductions in chemokines, inflammatory cells and DNA damage occurred in infected Egfr(Δepi) versus Egfr(fl/fl) control mice. In H. pylori-infected transgenic insulin-gastrin (INS-GAS) mice and gerbils, gefitinib treatment markedly reduced dysplasia and carcinoma. Gefitinib blocked H. pylori-induced activation of mitogen-activated protein kinase 1/3 (MAPK1/3) and activator protein 1 in gastric epithelial cells, resulting in inhibition of chemokine synthesis. MAPK1/3 phosphorylation and JUN activation was reduced in gastric tissues from infected wild-type and INS-GAS mice treated with gefitinib and in primary epithelial cells from Efgr(Δepi) versus Egfr(fl/fl) mice. Epithelial EGFR activation persisted in humans and mice after H. pylori eradication, and gefitinib reduced gastric carcinoma in INS-GAS mice treated with antibiotics. These findings suggest that epithelial EGFR inhibition represents a potential strategy to prevent development of gastric carcinoma in H. pylori-infected individuals. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  14. Helicobacter pylori induces vascular endothelial growth factor production in gastric epithelial cells through hypoxia-inducible factor-1α-dependent pathway.

    Science.gov (United States)

    Kang, Min-Jung; Song, Eun-Jung; Kim, Bo-Yeon; Kim, Dong-Jae; Park, Jong-Hwan

    2014-12-01

    Although Helicobacter pylori have been known to induce vascular endothelial growth factor (VEGF) production in gastric epithelial cells, the precise mechanism for cellular signaling is incompletely understood. In this study, we investigated the role of bacterial virulence factor and host cellular signaling in VEGF production of H. pylori-infected gastric epithelial cells. We evaluated production of VEGF, activation of nuclear factor nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinases (MAPKs) and hypoxia-inducible factor-1α (HIF-1α) stabilization in gastric epithelial cells infected with H. pylori WT or isogenic mutants deficient in type IV secretion system (T4SS). H. pylori induced VEGF production in gastric epithelial cells via both T4SS-dependent and T4SS-independent pathways, although T4SS-independent pathway seems to be the dominant signaling. The inhibitor assay implicated that activation of NF-κB and MAPKs is dispensable for H. pylori-induced VEGF production in gastric epithelial cells. H. pylori led to HIF-1α stabilization in gastric epithelial cells independently of T4SS, NF-κB, and MAPKs, which was essential for VEGF production in these cells. N-acetyl-cysteine (NAC), a reactive oxygen species (ROS) inhibitor, treatment impaired H. pylori-induced HIF-1α stabilization and VEGF production in gastric epithelial cells. We defined the important role of ROS-HIF-1α axis in VEGF production of H. pylori-infected gastric epithelial cells, and bacterial T4SS has a minor role in H. pylori-induced VEGF production of gastric epithelial cells. © 2014 John Wiley & Sons Ltd.

  15. Isocitrate dehydrogenase of Helicobacter pylori potentially induces humoral immune response in subjects with peptic ulcer disease and gastritis.

    Directory of Open Access Journals (Sweden)

    M Abid Hussain

    Full Text Available BACKGROUND: H. pylori causes gastritis and peptic ulcers and is a risk factor for the development of gastric carcinoma. Many of the proteins such as urease, porins, flagellins and toxins such as lipo-polysaccharides have been identified as potential virulence factors which induce proinflammatory reaction. We report immunogenic potentials of isocitrate dehydrogenase (ICD, an important house keeping protein of H. pylori. METHODOLOGY/PRINCIPAL FINDINGS: Amino acid sequences of H. pylori ICD were subjected to in silico analysis for regions with predictably high antigenic indexes. Also, computational modelling of the H. pylori ICD as juxtaposed to the E. coli ICD was carried out to determine levels of structure similarity and the availability of surface exposed motifs, if any. The icd gene was cloned, expressed and purified to a very high homogeneity. Humoral response directed against H. pylori ICD was detected through an enzyme linked immunosorbent assay (ELISA in 82 human subjects comprising of 58 patients with H. pylori associated gastritis or ulcer disease and 24 asymptomatic healthy controls. The H. pylori ICD elicited potentially high humoral immune response and revealed high antibody titers in sera corresponding to endoscopically-confirmed gastritis and ulcer disease subjects. However, urea-breath-test negative healthy control samples and asymptomatic control samples did not reveal any detectable immune responses. The ELISA for proinflammatory cytokine IL-8 did not exhibit any significant proinflammatory activity of ICD. CONCLUSIONS/SIGNIFICANCE: ICD of H. pylori is an immunogen which interacts with the host immune system subsequent to a possible autolytic-release and thereby significantly elicits humoral responses in individuals with invasive H. pylori infection. However, ICD could not significantly stimulate IL8 induction in a cultured macrophage cell line (THP1 and therefore, may not be a notable proinflammatory agent.

  16. Endoplasmic reticulum stress contributes to Helicobacter pylori VacA-induced apoptosis.

    Directory of Open Access Journals (Sweden)

    Yuko Akazawa

    Full Text Available Vacuolating cytotoxin A (VacA is one of the important virulence factors produced by H. pylori. VacA induces apoptotic cell death, which is potentiated by ammonia. VacA also causes cell death by mitochondrial damage, via signaling pathways that are not fully defined. Our aim was to determine whether endoplasmic reticulum (ER stress is associated with VacA-induced mitochondrial dysfunction and apoptosis. We found that C/EBP homologous protein (CHOP, a key signaling protein of ER stress-induced apoptosis, was transcriptionally up-regulated following incubation of gastric epithelial cells with VacA. The effect of VacA on CHOP induction was significantly enhanced by co-incubation with ammonium chloride. Phosphorylation of eukaryotic initiation factor 2 (eIF2-alpha, which is known to occur downstream of the ER stress sensor PKR-like ER-localized eIF2-alpha kinase (PERK and to regulate CHOP expression, was also observed following incubation with VacA in the presence of ammonium chloride. Knockdown of CHOP by siRNA resulted in inhibition of VacA-induced apoptosis. Further studies showed that silencing of the PERK gene with siRNA attenuated VacA-mediated phosphorylation of eIF2-alpha, CHOP induction, expression of BH3-only protein Bim and Bax activation, and cell death induced by VacA with ammonium chloride, indicating that ER stress may lead to mitochondrial dysfunction during VacA-induced toxicity. Activation of ER stress and up-regulation of BH3-only proteins were also observed in human H. pylori-infected gastric mucosa. Collectively, this study reveals a possible association between VacA-induced apoptosis in gastric epithelial cells, and activation of ER stress in H. pylori-positive gastric mucosa.

  17. Recombinant Helicobacter pylori catalase

    Institute of Scientific and Technical Information of China (English)

    Yang Bai; Ya-Li Zhang; Jian-Feng Jin; Ji-De Wang; Zhao-Shan Zhang

    2003-01-01

    AIM: To construct a recombinant strain which highly expresses catalase of Helicobacter pylori(H.pylori) and assay the activity of H. pylori catalase.METHODS: The catalase DNA was amplified from H. pylori chromosomal DNA with PCR techniques and inserted into the prokaryotie expression vector pET-22b (+), and then was transformed into the BL21 (DE3) E. coli strain which expressed catalase recombinant protein. The activity of H.pylori catalase was assayed by the Beers & Sizers.RESULTS: DNA sequence analysis showed that the sequence of catalase DNA was the same as GenBank's research. The catalase recombinant protein amounted to 24.4 % of the total bacterial protein after induced with IPTG for 3 hours at 37 ℃ and the activity of H. pylori catalase was high in the BL21 (DE3) E. coli strain.CONCLUSION: A clone expressing high activity H. pylori catalase is obtained, laying a good foundation for further studies.

  18. Helicobacter pylori-induced modulation of the promoter methylation of Wnt antagonist genes in gastric carcinogenesis.

    Science.gov (United States)

    Yang, Hyo-Joon; Kim, Sang Gyun; Lim, Joo Hyun; Choi, Ji Min; Kim, Woo Ho; Jung, Hyun Chae

    2017-06-22

    This study aimed to investigate the changes in the promoter methylation and gene expression of multiple Wnt antagonists between the chronic infection and eradication of Helicobacter pylori (H. pylori) in gastric carcinogenesis. The levels of methylation and corresponding mRNA expression of seven Wnt antagonist genes (SFRP1, -2, -5, DKK1, -2, -3, WIF1) were compared among the patients with H. pylori-positive gastric cancers (GCs), and H. pylori-positive and H. pylori-negative controls, by quantitative MethyLight assay and real-time reverse transcription (RT)-polymerase chain reaction (PCR), respectively. The changes of the methylation and expression levels of the genes were also compared between the H. pylori eradication and H. pylori-persistent groups 1 year after endoscopic resection of GCs. The methylation levels of SFRP and DKK family genes were significantly increased in the patients with H. pylori-positive GCs and followed by H. pylori-positive controls compared with H. pylori-negative controls (P pylori-negative controls, H. pylori-positive controls, and to H. pylori-positive GCs (P pylori eradication (P pylori-associated gastric carcinogenesis. The epigenetic field may not be reversed even after H. pylori eradication except by DKK3 methylation.

  19. Dual Roles of Helicobacter pylori NapA in inducing and combating oxidative stress.

    Science.gov (United States)

    Wang, Ge; Hong, Yang; Olczak, Adriana; Maier, Susan E; Maier, Robert J

    2006-12-01

    Neutrophil-activating protein (NapA) has been well documented to play roles in human neutrophil recruitment and in stimulating host cell production of reactive oxygen intermediates (ROI). A separate role for NapA in combating oxidative stress within H. pylori was implied by studies of various H. pylori mutant strains. Here, physiological analysis of a napA strain was the approach used to assess the iron-sequestering and stress resistance roles of NapA, its role in preventing oxidative DNA damage, and its importance to mouse colonization. The napA strain was more sensitive to oxidative stress reagents and to oxygen, and it contained fourfold more intracellular free iron and more damaged DNA than the parent strain. Pure, iron-loaded NapA bound to DNA, but native NapA did not, presumably linking iron levels sensed by NapA to DNA damage protection. Despite its in vitro phenotype of sensitivity to oxidative stress, the napA strain showed normal (like that of the wild type) mouse colonization efficiency in the conventional in vivo assay. By use of a modified mouse inoculation protocol whereby nonviable H. pylori is first inoculated into mice, followed by (live) bacterial strain administration, an in vivo role for NapA in colonization efficiency could be demonstrated. NapA is the critical component responsible for inducing host-mediated ROI production, thus inhibiting colonization by the napA strain. An animal colonization experiment with a mixed-strain infection protocol further demonstrated that the napA strain has significantly decreased ability to survive when competing with the wild type. H. pylori NapA has unique and separate roles in gastric pathogenesis.

  20. High dietary salt intake exacerbates Helicobacter pylori-induced gastric carcinogenesis.

    Science.gov (United States)

    Gaddy, Jennifer A; Radin, Jana N; Loh, John T; Zhang, Feng; Washington, M Kay; Peek, Richard M; Algood, Holly M Scott; Cover, Timothy L

    2013-06-01

    Persistent colonization of the human stomach with Helicobacter pylori is a risk factor for gastric adenocarcinoma, and H. pylori-induced carcinogenesis is dependent on the actions of a bacterial oncoprotein known as CagA. Epidemiological studies have shown that high dietary salt intake is also a risk factor for gastric cancer. To investigate the effects of a high-salt diet, we infected Mongolian gerbils with a wild-type (WT) cagA(+) H. pylori strain or an isogenic cagA mutant strain and maintained the animals on a regular diet or a high-salt diet. At 4 months postinfection, gastric adenocarcinoma was detected in 100% of the WT-infected/high-salt-diet animals, 58% of WT-infected/regular-diet animals, and none of the animals infected with the cagA mutant strain (P diet had more severe gastric inflammation, higher gastric pH, increased parietal cell loss, increased gastric expression of interleukin 1β (IL-1β), and decreased gastric expression of hepcidin and hydrogen potassium ATPase (H,K-ATPase) compared to those on a regular diet. Previous studies have detected upregulation of CagA synthesis in response to increased salt concentrations in the bacterial culture medium, and, concordant with the in vitro results, we detected increased cagA transcription in vivo in animals fed a high-salt diet compared to those on a regular diet. Animals infected with the cagA mutant strain had low levels of gastric inflammation and did not develop hypochlorhydria. These results indicate that a high-salt diet potentiates the carcinogenic effects of cagA(+) H. pylori strains.

  1. Compound 13, an α1-selective small molecule activator of AMPK, inhibits Helicobacter pylori-induced oxidative stresses and gastric epithelial cell apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Hangyong; Zhu, Huanghuang; Lin, Zhou; Lin, Gang; Lv, Guoqiang, E-mail: lvguoqiangwuxivip@163.com

    2015-08-07

    Half of the world's population experiences Helicobacter pylori (H. pylori) infection, which is a main cause of gastritis, duodenal and gastric ulcer, and gastric cancers. In the current study, we investigated the potential role of compound 13 (C13), a novel α1-selective small molecule activator of AMP-activated protein kinase (AMPK), against H. pylori-induced cytotoxicity in cultured gastric epithelial cells (GECs). We found that C13 induced significant AMPK activation, evidenced by phosphorylation of AMPKα1 and ACC (acetyl-CoA carboxylase), in both primary and transformed GECs. Treatment of C13 inhibited H. pylori-induced GEC apoptosis. AMPK activation was required for C13-mediated GEC protection. Inhibition of AMPK kinase activity by the AMPK inhibitor Compound C, or silencing AMPKα1 expression by targeted-shRNAs, alleviated C13-induced GEC protective activities against H. pylori. Significantly, C13 inhibited H. pylori-induced reactive oxygen species (ROS) production in GECs. C13 induced AMPK-dependent expression of anti-oxidant gene heme oxygenase (HO-1) in GECs. Zinc protoporphyrin (ZnPP) and tin protoporphyrin (SnPP), two HO-1 inhibitors, not only suppressed C13-mediated ROS scavenging activity, but also alleviated its activity in GECs against H. pylori. Together, these results indicate that C13 inhibits H. pylori-induced ROS production and GEC apoptosis through activating AMPK–HO–1 signaling. - Highlights: • We synthesized compound 13 (C13), a α1-selective small molecule AMPK activator. • C13-induced AMPK activation requires α1 subunit in gastric epithelial cells (GECs). • C13 enhances Helicobacter pylori-induced pro-survival AMPK activation to inhibit GEC apoptosis. • C13 inhibits H. pylori-induced reactive oxygen species (ROS) production in GECs. • AMPK-heme oxygenase (HO-1) activation is required for C13-mediated anti-oxidant activity.

  2. microRNA-155, induced by interleukin-1ß, represses the expression of microphthalmia-associated transcription factor (MITF-M in melanoma cells.

    Directory of Open Access Journals (Sweden)

    Nathalie Arts

    Full Text Available Loss of expression of surface antigens represents a significant problem for cancer immunotherapy. Microphthalmia-associated transcription factor (MITF-M regulates melanocyte fate by driving expression of many differentiation genes, whose protein products can be recognized by cytolytic T lymphocytes. We previously reported that interleukin-1ß (IL-1ß can downregulate MITF-M levels. Here we show that downregulation of MITF-M expression by IL-1ß was paralleled by an upregulation of miR-155 expression in four melanoma lines. We confirmed that miR-155 was able to target endogenous MITF-M in melanoma cells and demonstrated a role for miR-155 in the IL-1ß-induced repression of MITF-M by using an antagomiR. Notably, we also observed a strong negative correlation between MITF-M and miR-155 levels in a mouse model of melanoma. Taken together, our results indicate that MITF-M downregulation by inflammatory stimuli might be partly due to miR-155 upregulation. This could represent a novel mechanism of melanoma immune escape in an inflammatory microenvironment.

  3. Overexpression of c-fos in Helicobacter pylori-induced gastric precancerosis of Mongolian gerbil

    Institute of Scientific and Technical Information of China (English)

    Yong-Li Yang; Bo Xu; Yu-Gang Song; Wan-Dai Zhang

    2003-01-01

    AIM: To explore dysregulation of c-fos in several human malignancies, and to further investigate the role of c-fos in Helicobacter pylori ( H. pylori)-induced gastric precancerosis.METHODS: Four-week-old male Mongolian gerbils were H. pyloriNCTC 11 637 in Brucella broth were inoculated orally into 20 Mongolian gerbils. Another 20 gerbils were inoculated with Brucella broth as controls. 10 of the infected gerbils and 10 of the non- infected control gerbils were sacrificed at 25 and 45 weeks after infection. The stomach of each gerbil was removed and opened for macroscopic observation. The expression of c-fos was analyzed by RTPCR and immunohistochemical studies in H. pylori-induced gastric precancerosis of Mongolian gerbil. Half of each gastric antrum mucosa was dissected for RNA isolation and RTPCR. β-actin was used as the housekeeping gene and amplified with c-fos as contrast. PCR products of c-fos were analyzed by gel image system and the level of c-fos was reflected with the ratio of c-fos/β-actin. The immunostaining for c-foswas conducted using monoclonal antibody of c-fosand the StreptAvidin-Biotin-enzyme Complex kit.RESULTS: H. pyloriwas constantly found in all infected animals in this study. After infection of H. Pylorifor 25 weeks,ulcers were observed in the antral and the body of stomach of 60 % infected animals (6/10). Histological examination showed that all animals developed severe inflammation, especially in the area close to ulcers, and multifocal lymphoid follicles appeared in the lamina propria and submucosa. After infection of H. Pylorifor 45 weeks, severe atrophic gastritis in all infected animals, intestinal metaplasia in 80 % infected animals (8/10) and dysplasia in 60 % infected animals (6/10) could be observed. C-fos mRNA levels were significantlyhigher after infection of H. pylorifor 25 weeks (1.84±0.79),and for 45 weeks (1.59±0.37) than those in control-animals (0.74±0.22, P<0.01). C-fos mRNA levels were increased 2.5-fold by 25th

  4. Quantitative miR analysis in chronic lymphocytic leukaemia/small lymphocytic lymphoma - proliferation centres are characterized by high miR-92a and miR-155 and low miR-150 expression.

    Science.gov (United States)

    Szurián, Kinga; Csala, Irén; Piurkó, Violetta; Deák, Linda; Matolcsy, András; Reiniger, Lilla

    2017-07-01

    Proliferation centres (PCs) are histological hallmarks of lymph nodes in chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL). Chromosomal abnormalities have already been described to accumulate preferably in the PCs as opposed to the intervening small cell areas. To further characterize the pathogenic role of PCs, the expression levels of 17 selected miRs known to be involved in the development of CLL/SLL were compared in the PCs and the intervening small cell areas in lymph nodes of 15 patients with CLL/SLL. The miR expression levels were also compared to the cytogenetic alterations defined by FISH analysis. Our results show that two known oncomiRs, miR-155 and -92a were upregulated and the tumour suppressor miR-150 was downregulated in the PCs. Low expression of miR-150 was also associated with loss of 11q. In summary we found significantly higher expression of oncomiRs and lower expression of a tumour suppressor miR in PCs of CLL/SLL lymph nodes, which support the hypothesis that the PCs may drive the disease and play a role in progression. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Glycophenotypic alterations induced by Pteridium aquilinum in mice gastric mucosa: synergistic effect with Helicobacter pylori infection.

    Directory of Open Access Journals (Sweden)

    Joana Gomes

    Full Text Available The bracken fern Pteridium aquilinum is a plant known to be carcinogenic to animals. Epidemiological studies have shown an association between bracken fern exposure and gastric cancer development in humans. The biological effects of exposure to this plant within the gastric carcinogenesis process are not fully understood. In the present work, effects in the gastric mucosa of mice treated with Pteridium aquilinum were evaluated, as well as molecular mechanisms underlying the synergistic role with Helicobacter pylori infection. Our results showed that exposure to Pteridium aquilinum induces histomorphological modifications including increased expression of acidic glycoconjugates in the gastric mucosa. The transcriptome analysis of gastric mucosa showed that upon exposure to Pteridium aquilinum several glycosyltransferase genes were differently expressed, including Galntl4, C1galt1 and St3gal2, that are mainly involved in the biosynthesis of simple mucin-type carbohydrate antigens. Concomitant treatment with Pteridium aquilinum and infection with Helicobacter pylori also resulted in differently expressed glycosyltransferase genes underlying the biosynthesis of terminal sialylated Lewis antigens, including Sialyl-Lewis(x. These results disclose the molecular basis for the altered pattern of glycan structures observed in the mice gastric mucosa. The gene transcription alterations and the induced glycophenotypic changes observed in the gastric mucosa contribute for the understanding of the molecular mechanisms underlying the role of Pteridium aquilinum in the gastric carcinogenesis process.

  6. Effects of dietary calcium on Helicobacter pylori-induced gastritis in Mongolian gerbils.

    Science.gov (United States)

    Iimuro, Masaki; Nakamura, Shiro; Arakawa, Tetsuo; Wakabayashi, Keiji; Mutoh, Michihiro

    2013-09-01

    Helicobacter pylori (Hp) infection causes gastritis and is considered a gastric cancer risk factor. We have previously reported that codfish meal markedly enhanced Hp-induced gastritis in Mongolian gerbils. In the present study, we sought the responsible components in codfish meal. Codfish were divided into three parts (meat, viscera and 'other parts', including bone), and administered to Hp-infected gerbils. Subsequently, cod bone, sardine bone and prawn shell were tested, along with major calcium components, hydroxyapatite and calcium carbonate, in bone and shell, respectively. 'Other parts' and cod bone enhanced Hp-induced gastritis, as was observed for whole codfish. Similarly, sardine bone and prawn shell, as well as 0.22-0.88% hydroxyapatite and calcium carbonate, enhanced gastritis. In contrast, administration of a higher dose of the calcium compounds exerted protective effects. Intake of calcium compounds may contribute to enhancement of Hp-induced gastritis.

  7. Red wine and green tea reduce H pylori- or VacA-induced gastritis in a mouse model

    Institute of Scientific and Technical Information of China (English)

    Paolo Ruggiero; Giacomo Rossi; Francesco Tombola; Laura Pancotto; Laura Lauretti; Giuseppe Del Giudice; Mario Zoratti

    2007-01-01

    AIM: To investigate whether red wine and green tea could exert anti-H pylori or anti-VacA activity in vivo in a mouse model of experimental infection.METHODS: Ethanol-free red wine and green tea concentrates were administered orally as a mixture of the two beverages to H pylori infected mice, or separately to VacA-treated mice. Gastric colonization and gastric inflammation were quantified by microbiological,histopathological, and immunohistochemical analyses.RESULTS: In H pylori-infected mice, the red wine and green tea mixture significantly prevented gastritis and limited the localization of bacteria and VacA to the surface of the gastric epithelium. Similarly, both beverages significantly prevented gastric epithelium damage in VacA-treated mice; green tea, but not red wine, also altered the VacA localization in the gastric epithelium.CONCLUSION: Red wine and green tea are able to prevent H pylori-induced gastric epithelium damage,possibly involving VacA inhibition. This observation supports the possible relevance of diet on the pathological outcome of H pylori infection.

  8. N-acetylcysteine prevents the development of gastritis induced by Helicobacter pylori infection.

    Science.gov (United States)

    Jang, Sungil; Bak, Eun-Jung; Cha, Jeong-Heon

    2017-05-01

    Helicobacter pylori (H. pylori) is a human gastric pathogen, causing various gastric diseases ranging from gastritis to gastric adenocarcinoma. It has been reported that combining N-acetylcysteine (NAC) with conventional antibiotic therapy increases the success rate of H. pylori eradication. We evaluated the effect of NAC itself on the growth and colonization of H. pylori, and development of gastritis, using in vitro liquid culture system and in vivo animal models. H. pylori growth was evaluated in broth culture containing NAC. The H. pylori load and histopathological scores of stomachs were measured in Mongolian gerbils infected with H. pylori strain 7.13, and fed with NAC-containing diet. In liquid culture, NAC inhibited H. pylori growth in a concentration-dependent manner. In the animal model, 3-day administration of NAC after 1 week from infection reduced the H. pylori load; 6-week administration of NAC after 1 week from infection prevented the development of gastritis and reduced H. pylori colonization. However, no reduction in the bacterial load or degree of gastritis was observed with a 6-week administration of NAC following 6-week infection period. Our results indicate that NAC may exert a beneficial effect on reduction of bacterial colonization, and prevents the development of severe inflammation, in people with initial asymptomatic or mild H. pylori infection.

  9. Th immune response induced by H pylori vaccine with chitosan as adjuvant and its relation to immune protection

    Institute of Scientific and Technical Information of China (English)

    Yong Xie; Nan-Jin Zhou; Yan-Feng Gong; Xiao-Jiang Zhou; Jiang Chen; Si-Juan Hu; Nong-Hua Lu; Xiao-Hua Hou

    2007-01-01

    was significantly higher in the groups with chitosan as an adjuvant than in other groups without adjuvant (P < 0.05). After challenge, the level of IL-4 was significantly higher in the groups with chitosan particles as an adjuvant than in the group with CT as an adjuvant (P < 0.05), and in the group with chitosan solution as an adjuvant, the level of IL-4 was significantly higher than that in control group, non-adjuvant group and the groups with CT (P < 0.05 or 0.001). The ratio of anti- H pylori IgG2a/IgGl in serum was significantly lower in the groups with chitosan as an adjuvant than in the groups with CT as an adjuvant or without adjuvant (P < 0.01).CONCLUSION: H pylori vaccine with chitosan as an adjuvant can protect against H pylori infection and induce both Thl and Th2 type immune response.

  10. A C-Terminal Coiled-Coil Region of CagL is Responsible for Helicobacter Pylori-Induced Il-8 Expression.

    Science.gov (United States)

    Wiedemann, Tobias; Hofbaur, Stefan; Loell, Eva; Rieder, Gabriele

    2016-09-29

    Interleukin-8 (IL-8) is a potent neutrophil-activating chemokine which triggers the infiltration and migration of neutrophils into areas of bacterial infection. Helicobacter pylori-infected patient studies as well as animal models have revealed that H. pylori type I strains carrying an intact cytotoxin-associated gene pathogenicity island (cag-PAI) with a functional type IV secretion system (T4SS) induce IL-8 expression and secretion in gastric mucosa. This gastric mucosal IL-8 expression correlates with severe histological changes due to H. pylori infection. In the present study, we explored a new recognition pattern on the bacterial adhesion protein CagL inducing IL-8 expression in H. pylori-infected host cells. To analyze the secreted IL-8 concentration, we performed IL-8 enzyme-linked immunosorbent assay (ELISA). To investigate the H. pylori-induced IL-8 expression on the transcriptional level, we transiently transfected gastric epithelial cells (AGS) with a human IL-8 luciferase reporter construct. The results of this study demonstrate that specifically the C-terminal coiled-coil region of the H. pylori CagL protein, a protein described to be located on the tip of the T4SS-pilus, is responsible for several in vitro observations: 1) H. pylori-induced IL-8 secretion via the transforming growth factor (TGF)-α activated epidermal growth factor-receptor (EGF-R) signaling pathway; 2) H. pylori-induced elongation of the cells, a typical CagA-induced phenotype; and 3) the bridging of the T4SS to its human target cells. This novel bacterial-host recognition sequence allows a new insight into how H. pylori induces the inflammatory response in gastric epithelial cells and facilitates the development of precancerous conditions.

  11. A C-Terminal Coiled-Coil Region of CagL is Responsible for Helicobacter Pylori-Induced Il-8 Expression

    Science.gov (United States)

    Wiedemann, Tobias; Hofbaur, Stefan; Loell, Eva; Rieder, Gabriele

    2016-01-01

    Interleukin-8 (IL-8) is a potent neutrophil-activating chemokine which triggers the infiltration and migration of neutrophils into areas of bacterial infection. Helicobacter pylori-infected patient studies as well as animal models have revealed that H. pylori type I strains carrying an intact cytotoxin-associated gene pathogenicity island (cag-PAI) with a functional type IV secretion system (T4SS) induce IL-8 expression and secretion in gastric mucosa. This gastric mucosal IL-8 expression correlates with severe histological changes due to H. pylori infection. In the present study, we explored a new recognition pattern on the bacterial adhesion protein CagL inducing IL-8 expression in H. pylori-infected host cells. To analyze the secreted IL-8 concentration, we performed IL-8 enzyme-linked immunosorbent assay (ELISA). To investigate the H. pylori-induced IL-8 expression on the transcriptional level, we transiently transfected gastric epithelial cells (AGS) with a human IL-8 luciferase reporter construct. The results of this study demonstrate that specifically the C-terminal coiled-coil region of the H. pylori CagL protein, a protein described to be located on the tip of the T4SS-pilus, is responsible for several in vitro observations: 1) H. pylori-induced IL-8 secretion via the transforming growth factor (TGF)-α activated epidermal growth factor-receptor (EGF-R) signaling pathway; 2) H. pylori-induced elongation of the cells, a typical CagA-induced phenotype; and 3) the bridging of the T4SS to its human target cells. This novel bacterial-host recognition sequence allows a new insight into how H. pylori induces the inflammatory response in gastric epithelial cells and facilitates the development of precancerous conditions. PMID:27766167

  12. Helicobacter pylori VacA suppresses Lactobacillus acidophilus-induced interferon beta signaling in macrophages via alterations in the endocytic pathway.

    Science.gov (United States)

    Weiss, Gudrun; Forster, Sam; Irving, Aaron; Tate, Michelle; Ferrero, Richard L; Hertzog, Paul; Frøkiær, Hanne; Kaparakis-Liaskos, Maria

    2013-06-11

    Helicobacter pylori causes chronic gastritis and avoids elimination by the immune system of the infected host. The commensal bacterium Lactobacillus acidophilus has been suggested to exert beneficial effects as a supplement during H. pylori eradication therapy. In the present study, we applied whole-genome microarray analysis to compare the immune responses induced in murine bone marrow-derived macrophages (BMDMs) stimulated with L. acidophilus, H. pylori, or both bacteria in combination. While L. acidophilus induced a Th1-polarizing response characterized by high expression of interferon beta (IFN-β) and interleukin 12 (IL-12), H. pylori strongly induced the innate cytokines IL-1β and IL-1α. In BMDMs prestimulated with L. acidophilus, H. pylori blocked the expression of L. acidophilus-induced IFN-β and IL-12 and suppressed the expression of key regulators of the Rho, Rac, and Cdc42 GTPases. The inhibition of L. acidophilus-induced IFN-β was independent of H. pylori viability and the virulence factor CagPAI; however, a vacuolating cytotoxin (vacA) mutant was unable to block IFN-β. Confocal microscopy demonstrated that the addition of H. pylori to L. acidophilus-stimulated BMDMs redirects intracellular processing, leading to an accumulation of L. acidophilus in the endosomal and lysosomal compartments. Thus, our findings indicate that H. pylori inhibits the development of a strong Th1-polarizing response in BMDMs stimulated with L. acidophilus by blocking the production of IFN-β in a VacA-dependent manner. We suggest that this abrogation is caused by a redirection of the endocytotic pathway in the processing of L. acidophilus. IMPORTANCE Approximately half of the world's population is infected with Helicobacter pylori. The factors that allow this pathogen to persist in the stomach and cause chronic infections have not yet been fully elucidated. In particular, how H. pylori avoids killing by macrophages, one of the main types of immune cell underlying the

  13. Helicobacter pylori-induced activation of β-catenin involves low density lipoprotein receptor-related protein 6 and Dishevelled

    Directory of Open Access Journals (Sweden)

    Lendeckel Uwe

    2010-02-01

    Full Text Available Abstract Background The human microbial pathogen Helicobacter pylori resides in the stomach of about fifty percent of the world's population and represents a risk factor for chronic gastritis, peptic ulcers and, in rare cases, gastric cancer. Alterations of the Wnt/β-catenin signaling pathway have been described in almost every human cancer disease, due to the regulation of target genes being involved in cell cycle control, differentiation, cell migration or stem cell control. Our study aimed to elucidate the role of proximal Wnt signaling components low density lipoprotein receptor-related protein 6 (LRP6 and Dishevelled (Dvl in the activation of β-catenin early after infection of gastric epithelial cells with H. pylori. Results Infection of gastric epithelial NCI-N87 cells with H. pylori induces rapid phosphorylation of the Wnt/β-catenin pathway co-receptor LRP6 independent of the cytotoxin-associated gene A (CagA or vacuolating cytotoxin A (VacA. However, bacteria lacking a functional type 4 secretion system (T4SS failed to induce LRP6 phosphorylation. Further, we identified proteins of the Dvl family, namely Dvl2 and Dvl3, which are involved in LRP6 phosphorylation. H. pylori-induced nuclear accumulation of β-catenin and its transcriptional activation, and expression of Wnt target genes are strongly reduced in stable knockdown cell lines deficient for LRP6, Dvl2 or Dvl3. Conclusion We analysed the H. pylori-induced activation of Wnt-signaling factors and demonstrate for the first time that the canonical Wnt-signaling proteins LRP6 and Dvl2 and Dvl3 are involved in the regulation of β-catenin.

  14. Helicobacter pylori-induced sonic hedgehog expression is regulated by NFκB pathway activation: The use of a novel in vitro model to study epithelial response to infection

    OpenAIRE

    Schumacher, MA; R. Feng; Aihara, E; Engevik, AC; Montrose, MH; Ottemann, KM; Zavros, Y

    2015-01-01

    © 2014 John Wiley & Sons Ltd. Helicobacter pylori (H. pylori) infection leads to acute induction of Sonic Hedgehog (Shh) in the stomach that is associated with the initiation of gastritis. The mechanism by which H. pylori induces Shh is unknown. Shh is a target gene of transcription factor Nuclear Factor-κB (NFκB). We hypothesize that NFκB mediates H. pylori-induced Shh. Materials and Methods: To visualize Shh ligand expression in response to H. pylori infection in vivo, we used a mouse model...

  15. Differential effects of multiplicity of infection on Helicobacter pylori-induced signaling pathways and interleukin-8 gene transcription.

    Science.gov (United States)

    Ritter, Birgit; Kilian, Petra; Reboll, Marc Rene; Resch, Klaus; DiStefano, Johanna Kay; Frank, Ronald; Beil, Winfried; Nourbakhsh, Mahtab

    2011-02-01

    Interleukin-8 (IL-8) plays a central role in the pathogenesis of Helicobacter pylori infection. We used four different H. pylori strains isolated from patients with gastritis or duodenal ulcer disease to examine their differential effects on signaling pathways and IL-8 gene response in gastric epithelial cells. IL-8 mRNA level is elevated in response to high (100) multiplicity of infection (MOI) independent of cagA, vacA, and dupA gene characteristics. By lower MOIs (1 or 10), only cagA ( + ) strains significantly induce IL-8 gene expression. This is based on differential regulation of IL-8 promoter activity. Analysis of intracellular signaling pathways indicates that H. pylori clinical isolates induce IL-8 gene transcription through NF-κB p65, but by a MOI-dependent differential activation of MAPK pathways. Thus, the major virulence factors of H. pylori CagA, VacA, and DupA might play a minor role in the level of IL-8 gene response to a high bacterial load.

  16. miR-21、miR-155在乳腺癌患者血液与肿瘤组织中表达水平的相关性研究%Correlation study of the expression of miR-21 and miR-155 in the blood and tumor tissue of patients with breast cancer

    Institute of Scientific and Technical Information of China (English)

    卞国奉; 陈爱军

    2012-01-01

    目的 对健康女性血清及乳腺癌患者血清中miR-21和miR-155表达水平进行实时定量PCR检测,同肿瘤患者癌组织与对应癌旁组织的miR-21和miR-155表达水平的变化趋势相比较,以评价血清中miR-21和miR-155在乳腺癌早期诊断中的潜在价值.方法 收集健康女性血液和患者血液与患者癌组织和癌旁组织,利用实时荧光定量PCR对提取的RNA miR-21和miR-155进行相对定量检测,得到miR-21和miR-155在血清中变化趋势与在组织中变化趋势的相关性.结果 miR-21和miR-155在肿瘤组织的表达水平明显高于其在癌旁组织的表达水平,miR-21和miR-155在乳腺癌患者血清中的表达水平也要高于其在健康体检者血清中的表达水平.血清中miR-21和miR-155表达水平变化趋势与组织中miR-21和miR-155表达水平变化趋势一致.结论 血清中miR-21和miR-155能反映乳腺癌的发生,miR-21和miR-155有可能作为乳腺癌早期诊断的肿瘤标志物.%Objective To evaluate the expression levels of miR-21 and miR-155 in the serum of breast cancer patients and healthy women by real-time quantitative PCR, compared with the variation trend of the expression level of miR-21 and miR-155 in tumor tissue samples. Methods The samples were collected from the intraoperative tumor tissue, adjacent tissue, and the peripheral blood of patients and from the peripheral blood of healthy women. The miR-21 and miR-155 obtained were detected by real time quantitative PCR. Then the relationship between the trend of miR-21 and miR-155 in serum and in tumor tissues was analyzed. Results The expression levels of miR-21 and miR-155 in adjacent tissues of breast cancer patients were significantly lower than those in tumor tissues. The expression levels of miR-21 and miR-155 in the serum of breast cancer patients were significantly higher than those of healthy women. Conclusion The levels of serum miR-21 and miR-155 can be used as biomarkers for the early diagnosis of breast cancer.

  17. Helicobacter pylori Infection Induces Genetic Instability of Nuclear and Mitochondrial DNA in Gastric Cells

    DEFF Research Database (Denmark)

    Machado, Ana Manuel; Figueiredo, Ceu; Touati, Eliette;

    2009-01-01

    Purpose: Helicobacter pylori is a major cause of gastric carcinoma. To investigate a possible link between bacterial infection and genetic instability of the host genome, we examined the effect of H. pylori infection on known cellular repair pathways in vitro and in vivo. Moreover, various types...... of genetic instabilities in the nuclear and mitochondrial DNA (mtDNA) were examined. Experimental Design: We observed the effects of H pylori infection on a gastric cell line (AGS), on C57BL/6 mice, and on individuals with chronic gastritis. In AGS cells, the effect of H pylori infection on base excision...... cells and chronic gastritis tissue were determined by PCR, single-stranded conformation polymorphism, and sequencing. H pylori vacA and cagA genotyping was determined by multiplex PCR and reverse hybridization. Results: Following H pylori infection, the activity and expression of base excision repair...

  18. Host-pathogen systems biology: logical modelling of hepatocyte growth factor and Helicobacter pylori induced c-Met signal transduction

    Directory of Open Access Journals (Sweden)

    Kähne Thilo

    2008-01-01

    Full Text Available Abstract Background The hepatocyte growth factor (HGF stimulates mitogenesis, motogenesis, and morphogenesis in a wide range of tissues, including epithelial cells, on binding to the receptor tyrosine kinase c-Met. Abnormal c-Met signalling contributes to tumour genesis, in particular to the development of invasive and metastatic phenotypes. The human microbial pathogen Helicobacter pylori can induce chronic gastritis, peptic ulceration and more rarely, gastric adenocarcinoma. The H. pylori effector protein cytotoxin associated gene A (CagA, which is translocated via a type IV secretion system (T4SS into epithelial cells, intracellularly modulates the c-Met receptor and promotes cellular processes leading to cell scattering, which could contribute to the invasiveness of tumour cells. Using a logical modelling framework, the presented work aims at analysing the c-Met signal transduction network and how it is interfered by H. pylori infection, which might be of importance for tumour development. Results A logical model of HGF and H. pylori induced c-Met signal transduction is presented in this work. The formalism of logical interaction hypergraphs (LIH was used to construct the network model. The molecular interactions included in the model were all assembled manually based on a careful meta-analysis of published experimental results. Our model reveals the differences and commonalities of the response of the network upon HGF and H. pylori induced c-Met signalling. As another important result, using the formalism of minimal intervention sets, phospholipase Cγ1 (PLCγ1 was identified as knockout target for repressing the activation of the extracellular signal regulated kinase 1/2 (ERK1/2, a signalling molecule directly linked to cell scattering in H. pylori infected cells. The model predicted only an effect on ERK1/2 for the H. pylori stimulus, but not for HGF treatment. This result could be confirmed experimentally in MDCK cells using a specific

  19. Changes in gastric microbiota induced by Helicobacter pylori infection and preventive effects of Lactobacillus plantarum ZDY 2013 against such infection.

    Science.gov (United States)

    Pan, Mingfang; Wan, Cuixiang; Xie, Qiong; Huang, Renhui; Tao, Xueying; Shah, Nagendra P; Wei, Hua

    2016-02-01

    Helicobacter pylori is a gram-negative pathogen linked to gastric ulcers and stomach cancer. Gastric microbiota might play an essential role in the pathogenesis of these stomach diseases. In this study, we investigated the preventive effect of a probiotic candidate Lactobacillus plantarum ZDY 2013 as a protective agent against the gastric mucosal inflammation and alteration of gastric microbiota induced by H. pylori infection in a mouse model. Prior to infection, mice were pretreated with or without 400 µL of L. plantarum ZDY 2013 at a concentration of 10(9) cfu/mL per mouse. At 6 wk postinfection, gastric mucosal immune response and alteration in gastric microbiota mice were examined by quantitative real-time PCR and high-throughput 16S rRNA gene amplicon sequencing, respectively. The results showed that L. plantarum ZDY 2013 pretreatment prevented increase in inflammatory cytokines (e.g., IL-1β and IFN-γ) and inflammatory cell infiltration in gastric lamina propria induced by H. pylori infection. Weighted UniFrac principal coordinate analysis showed that L. plantarum ZDY 2013 pretreatment prevented the alteration in gastric microbiota post-H. pylori infection. Linear discriminant analysis coupled with effect size identified 22 bacterial taxa (e.g., Pasteurellaceae, Erysipelotrichaceae, Halomonadaceae, Helicobacteraceae, and Spirochaetaceae) that overgrew in the gastric microbiota of H. pylori-infected mice, and most of them belonged to the Proteobacteria phylum. Lactobacillus plantarum ZDY 2013 pretreatment prevented this alteration; only 6 taxa (e.g., Lachnospiraceae, Ruminococcaceae, and Clostridiaceae), mainly from the taxa of Firmicutes and Bacteroidetes, were dominant in the gastric microbiota of the L. plantarum ZDY 2013 pretreated mice. Administration of L. plantarum ZDY 2013 for 3 wk led to increase in several bacterial taxa (e.g., Rikenella, Staphylococcus, Bifidobacterium), although a nonsignificant alteration was found in the gastric microbiota

  20. Helicobacter pylori induces activation of human peripheral γδ+ T lymphocytes.

    Directory of Open Access Journals (Sweden)

    Benedetta Romi

    Full Text Available Helicobacter pylori is a gram-negative bacterium that causes gastric and duodenal diseases in humans. Despite a robust antibody and cellular immune response, H. pylori infection persists chronically. To understand if and how H. pylori could modulate T cell activation, in the present study we investigated in vitro the interaction between H. pylori and human T lymphocytes freshly isolated from peripheral blood of H. pylori-negative donors. A direct interaction of live, but not killed bacteria with purified CD3+ T lymphocytes was observed by microscopy and confirmed by flow cytometry. Live H. pylori activated CD3+ T lymphocytes and predominantly γδ+ T cells bearing the TCR chain Vδ2. Upon interaction with H. pylori, these cells up-regulated the activation molecule CD69 and produced cytokines (such as TNFα, IFNγ and chemokines (such as MIP-1β, RANTES in a non-antigen-specific manner. This activation required viable H. pylori and was not exhibited by other gram-negative bacteria. The cytotoxin-associated antigen-A (CagA, was at least partially responsible of this activation. Our results suggest that H. pylori can directly interact with T cells and modulate the response of γδ+ T cells, thereby favouring an inflammatory environment which can contribute to the chronic persistence of the bacteria and eventually to the gastric pathology.

  1. Effect of quercetin and its metabolites isorhamnetin and quercetin-3-glucuronide on inflammatory gene expression: role of miR-155.

    Science.gov (United States)

    Boesch-Saadatmandi, Christine; Loboda, Agnieszka; Wagner, Anika E; Stachurska, Anna; Jozkowicz, Alicja; Dulak, Jozef; Döring, Frank; Wolffram, Siegfried; Rimbach, Gerald

    2011-03-01

    In the present study the effect of quercetin and its major metabolites quercetin-3-glucuronide (Q3G) and isorhamnetin on inflammatory gene expression was determined in murine RAW264.7 macrophages stimulated with lipopolysaccharide. Quercetin and isorhamnetin but not Q3G significantly decreased mRNA and protein levels of tumor necrosis factor alpha. Furthermore a significant decrease in mRNA levels of interleukin 1β, interleukin 6, macrophage inflammatory protein 1α and inducible nitric oxide synthase was evident in response to the quercetin treatment. However Q3G did not affect inflammatory gene expression. Anti-inflammatory properties of quercetin and isorhamnetin were accompanied by an increase in heme oxygenase 1 protein levels, a downstream target of the transcription factor Nrf2, known to antagonize chronic inflammation. Furthermore, proinflammatory microRNA-155 was down-regulated by quercetin and isorhamnetin but not by Q3G. Finally, anti-inflammatory properties of quercetin were confirmed in vivo in mice fed quercetin-enriched diets (0.1 mg quercetin/g diet) over 6 weeks.

  2. Lactobacilli inhibit interleukin-8 production induced by Helicobacter pylori lipopolysaccharide-activated Toll-like receptor 4

    Institute of Scientific and Technical Information of China (English)

    Chao Zhou; Feng-Zhen Ma; Xue-Jie Deng; Hong Yuan; Hong-Sheng Ma

    2008-01-01

    AIM: To investigate the effect of Lactobacillus bulgaricus (LBG) on the Toll-like receptor 4 (TLR4) pathway and interleukin-8 (IL-8) production in SGC-7901 cells treated with Helicobacter pyloriSydney strain 1 lipopolysaccharide (H pyloriSS1-LPS).METHODS: SGC-7901 cells were treated with H pyIoriSS1-LPS in the presence or absence of pretreatment for 1 h with viable LBG or supematant recovered from LBG culture MRS broth (LBG-s). Cellular lysates were prepared for Western blot with anti-TLR4,anti-transforming growth factor β-activated kinase 1 (TAK1), anti-phospho-TAK1, anti-nuclear factor κB (NF-κB), anti-p38 mitogen-activated protein kinase (p38MAPK), and anti-phospho-p38MAPK antibodies.The amount of IL-8 in cell culture medium was measured by ELISA.RESULTS: H pyloriSS1-LPS up-regulated the expression of TLR4, stimulated the phosphorylation of TAK1, subsequently enhanced the activation of NFκB and the phosphorylation of p38MAPK in a timedependent manner, leading to augmentation of IL-8 production in SGC-7901 cells. Viable LBG or LBG-s pretreatment attenuated the expression of TLR4,inhibited the phosphorylation of TAK1 and p38MAPK,prevented the activation of NF-κB, and consequently blocked IL-8 production.CONCLUSION: H pyloriSS1-LPS induces IL-8production through activating TLR4 signaling in SGC-7901 cells and viable LBG or LBG-s prevents H pyloriSS1-LPS-mediated IL-8 production via inhibition of the TLR4 pathway.

  3. RAD51 G135C genetic polymorphism and their potential role in gastric cancer induced by Helicobacter pylori infection in Bhutan.

    Science.gov (United States)

    Trang, T T H; Nagashima, H; Uchida, T; Mahachai, V; Vilaichone, R-K; Tshering, L; Binh, T T; Yamaoka, Y

    2016-01-01

    In order to evaluate the role of the RAD51 G135C genetic polymorphism on the risk of gastric cancer induced by Helicobacter pylori infection, we determined allele frequency and genotype distribution of this polymorphism in Bhutan--a population documented with high prevalence of gastric cancer and extremely high prevalence of H. pylori infection. The status of RAD51 G135C was examined by restriction fragment length polymorphism analysis of PCR amplified fragments and sequencing. Histological scores were evaluated according to the updated Sydney system. G135C carriers showed significantly higher scores for intestinal metaplasia in the antrum than G135G carriers [mean (median) 0·33 (0) vs. 0·08 (0), P = 0·008]. Higher scores for intestinal metaplasia of G135C carriers compared to those of G135G carriers were also observed in H. pylori-positive patients [0·3 (0) vs. 0·1 (0), P = 0·002] and H. pylori-positive patients with gastritis [0·4 (0) vs. 0·1 (0), P = 0·002] but were not found in H. pylori-negative patients. Our findings revealed that a combination of H. pylori infection and RAD51 G135C genotype of the host showed an increasing score for intestinal metaplasia. Therefore, RAD51 G135C might be the important predictor for gastric cancer of H. pylori-infected patients.

  4. Helicobacter pylori induces in-vivo expansion of human regulatory T cells through stimulating interleukin-1β production by dendritic cells.

    Science.gov (United States)

    Mitchell, P J; Afzali, B; Fazekasova, H; Chen, D; Ali, N; Powell, N; Lord, G M; Lechler, R I; Lombardi, G

    2012-12-01

    Helicobacter pylori is one of the most common infections in the world. Despite inciting inflammation, immunological clearance of the pathogen is often incomplete. CD4(+) CD25(hi) forkhead box protein 3 (FoxP3(+)) regulatory T cells (T(regs)) are potent suppressors of different types of immune responses and have been implicated in limiting inflammatory responses to H. pylori. Investigating the influence of H. pylori on T(reg) function and proliferation, we found that H. pylori-stimulated dendritic cells (DCs) induced proliferation in T(regs) and impaired their suppressive capability. This effect was mediated by interleukin (IL)-1β produced by H. pylori-stimulated DCs. These data correlated with in-vivo observations in which H. pylori(+) gastric mucosa contained more T(regs) in active cell division than uninfected stomachs. Inciting local proliferation of T(regs) and inhibiting their suppressive function may represent a mechanism for the chronic gastritis and carcinogenesis attributable to H. pylori.

  5. Inhibition of Helicobacter pylori CagA-Induced Pathogenesis by Methylantcinate B from Antrodia camphorata

    Directory of Open Access Journals (Sweden)

    Chun-Jung Lin

    2013-01-01

    Full Text Available The bacterial pathogen Helicobacter pylori (Hp is the leading risk factor for the development of gastric cancer. Hp virulence factor, cytotoxin-associated gene A (CagA interacted with cholesterol-enriched microdomains and leads to induction of inflammation in gastric epithelial cells (AGS. In this study, we identified a triterpenoid methylantcinate B (MAB from the medicinal mushroom Antrodia camphoratawhich inhibited the translocation and phosphorylation of CagA and caused a reduction in hummingbird phenotype in HP-infected AGS cells. Additionally, MAB suppressed the Hp-induced inflammatory response by attenuation of NF-κB activation, translocation of p65 NF-κB, and phosphorylation of IκB-α, indicating that MAB modulates CagA-mediated signaling pathway. Additionally, MAB also suppressed the IL-8 luciferase activity and its secretion in HP-infected AGS cells. On the other hand, molecular structure simulations revealed that MAB interacts with CagA similarly to that of cholesterol. Moreover, binding of cholesterol to the immobilized CagA was inhibited by increased levels of MAB. Our results demonstrate that MAB is the first natural triterpenoid which competes with cholesterol bound to CagA leading to attenuation of Hp-induced pathogenesis of epithelial cells. Thus, this study indicates that MAB may have a scope to develop as a therapeutic candidate against Hp CagA-induced inflammation.

  6. Helicobacter pylori induces Snail expression through ROS-mediated activation of Erk and inactivation of GSK-3β in human gastric cancer cells.

    Science.gov (United States)

    Ngo, Hoang-Kieu-Chi; Lee, Hee Geum; Piao, Juan-Yu; Zhong, Xiancai; Lee, Ha-Na; Han, Hyeong-Jun; Kim, Wonki; Kim, Do-Hee; Cha, Young-Nam; Na, Hye-Kyung; Surh, Young-Joon

    2016-12-01

    Helicobacter pylori (H. pylori) infection has been known to be implicated in human gastric carcinogenesis. Snail, the zinc-finger transcription factor known as a key inducer of changes in the cell shape and morphogenetic movement, is aberrantly overexpressed and correlates with lymph node metastasis in gastric cancer. In the present study, we investigated whether H. pylori could induce Snail activation to provoke these changes. Using a cell scatter assay, we noticed that human gastric cancer AGS cells infected with H. pylori underwent morphological changes as well as disruption of cell-cell interaction, which was then reversed by silencing of Snail by use of small interfering RNA (siRNA). In addition, infection with H. pylori resulted in an increased intracellular level of Snail in gastric cancer cells, which was abrogated in the presence of U0126 and LY294002, inhibitors of MEK/Erk and PI3K/Akt pathways, respectively. Cycloheximide pulse-chase experiments coupled with immunocytochemical analysis revealed that the induction of Snail by H. pylori was regulated at multiple levels, including increased transcription of Snail mRNA, inhibition of protein degradation, and enhancement of nuclear translocation of Snail. Pre-treatment of AGS cells with N-acetylcysteine, a well-known reactive oxygen species (ROS) scavenger, attenuated the H. pylori-induced activation of Erk, its binding to Snail promoter, inactivation of GSK-3β, and accumulation of Snail. Collectively, these findings suggest that the upregulation of Snail expression induced by H. pylori and transformation to a spindle-like shape as a consequence in gastric cancer cells are attributable to ROS-mediated activation of Erk and the inhibition of GSK-3β signaling. © 2016 Wiley Periodicals, Inc.

  7. 淋巴瘤患者血浆中miR-21、miR-155、miR-210的表达及临床意义%The expression and clinical significance of miR-21,miR-155,miR-210 of plasma lymphoma patients

    Institute of Scientific and Technical Information of China (English)

    曹慧琴; 韦玮

    2016-01-01

    目的:探讨 miR-21、miR-155、miR-210的临床表达意义及其与淋巴瘤病理特征的相关性。方法采用RT-PCR 技术及免疫组化法测定60例行淋巴瘤患者血清中 miR-21、miR-155、miR-210表达量及 BCL-6蛋白水平,并对其与淋巴瘤病理特征相关性进行分析。结果与正常对照组相比,淋巴瘤患者 miR-21、miR-155、miR-210表达量显著提高,差异有统计学意义(P <0.05)。经相关分析可知,miR-21、miR-155表达量与免疫分型、MYC 基因、BCL-6蛋白有关,而 miR-210表达量则与免疫分型、MYC 基因有关。结论miR-21、miR-155、miR-210可能与淋巴瘤发生及进展相关。通过测定 miR-21、miR-155、miR-210表达情况可有效预测淋巴瘤病情的进展,对临床淋巴瘤诊治具有重要的指导意义。%Objective To investigate the expression and clinical significance of miR-21,miR-155,miR-210 of plasma lymphoma patients.Methods The expression levels of miR-21,miR-155,miR-210 and BCL-6 protein of 60 cases of plasma lymphoma patients were measured with RT-PCR and immunohistochemical staining,the features associated with lymphoma were analyzed.Results The levels of miR-21,miR-155,miR-210 of plasma lymphoma patients were higher than control group(P <0.05).The expression of miR-21,miR-155 were relationship with immune typing,MYC gene, BCL-6 protein,whereas the expression of miR-210 were relationship with immune typing,MYC genes.Conclusion miR-21,miR-155,miR-210 may occur and progress associated with lymphoma.By measuring miR-21,miR-155,miR-210 expression can predict disease progression of lymphoma,has important significance for clinical diagnosis and treatment of lymphoma.

  8. Helicobacter pylori Induces Serine Phosphorylation of EGFR via Novel TAK1-p38 Activation Pathway in an HB-EGF-Independent Manner.

    Science.gov (United States)

    Zaidi, Syed Faisal; Refaat, Alaa; Zhou, Yue; Sualeh Muhammad, Jibran; Shin, Myoung-Sook; Saiki, Ikuo; Sakurai, Hiroaki; Sugiyama, Toshiro

    2015-10-01

    The interaction of Helicobacter pylori with gastric epithelial cells can result in the activation of transcription factor NF-κB via TGF-β-activated kinase 1 (TAK1). In this study, we have demonstrated the role of H. pylori in the activation of EGFR via TAK1-mediated phosphorylation of p38. Gastric epithelial AGS or MKN-45 cells were co-cultured with wild-type or cagA(-) H. pylori strains. H. pylori was added to the cells, and the activation of EGFR, p65 (NF-κB) subunit, p38, ERK, and TAK1 was examined by Western blotting. Infected cells were pretreated with or without ligands, chemical inhibitors, anti-HB-EGF antibody, and siRNAs to evaluate the effects on phosphorylation of various EGFR residues. Fluorescence microscopy and flow cytometry were performed to detect the internalization of EGFR. Incubating cells with wild-type and CagA(-) H. pylori strains resulted in the rapid and transient phosphorylation of serine residues of EGFR. RNAi experiments using siRNA against TAK1 and p38 pathways blocked the phosphorylation of serine residue. Immunofluorescence and flow cytometry revealed that EGFR was internalized in H. pylori-infected cells after EGFR phosphorylation in a p38-dependent manner. In contrast, pretreatment with gefitinib and anti-HB-EGF antibody did not block both the phosphorylation and internalization of EGFR. Helicobacter pylori induces internalization of EGFR via novel TAK1-p38-serine activation pathway which is independent of HB-EGF. The interaction between TAK1 and EGFR in H. pylori-infected cells might open new dimensions in understanding H. pylori-associated gastric carcinogenesis. © 2015 John Wiley & Sons Ltd.

  9. Virulence and potential pathogenicity of coccoid Helicobacter pylori induced by antibiotics

    Science.gov (United States)

    She, Fei-Fei; Su, Dong-Hui; Lin, Jian-Yin; Zhou, Lin-Ying

    2001-01-01

    AIM: To explore the virulence and the potential pathogenicity of coccoid Helicobacter pylori (H. pylori) transformed from spiral form by exposure to antibiotic. METHODS: Three strains of H. pylori, isolated from gastric biopsy specimens of confirmed peptic ulcer, were converted from spiral into coccoid from by exposure to metronidazole. Both spiral and coccoid form of H. pylori were tested for the urease activity, the adherence to Hep 2 cells and the vacuolating cytotoxicity to Hela cells, and the differences of the protein were analysed by SDS-PAGE and Western blot. The mutation of the genes including ureA, ureB, hpaA, vacA and cagA, related with virulence, was detected by means of PCR and PCR-SSCP. RESULTS: In the coccoid H. pylori, the urease activity, the adherence to Hep 2 cells and the vacuolating cytotoxicity to Hela cells alldecreased. In strain F44, the rate and index of adherence reduced from 70.0% ± 5.3% to 33% ± 5.1% and from 2.6 ± 0.4 to 0.96 ± 0.3 (P hpaA or vacA. CONCLUSION: The virulence and the proteins with molecular weight over Mr 74000 in coccoid H.pylori decrease, but no deletion exists in amplification fragments from ureA, ureB, hpaA, vacA and cagA genes, suggesting that coccoid H.pylori may have potential pathogenicity. PMID:11819770

  10. Analysis of T4SS-induced signaling by H. pylori using quantitative phosphoproteomics

    National Research Council Canada - National Science Library

    Glowinski, Frithjof; Holland, Carsten; Thiede, Bernd; Jungblut, Peter R; Meyer, Thomas F

    2014-01-01

    .... A major virulence determinant of H. pylori is the type IV secretion system (T4SS), which is used to inject the virulence factor CagA into the host cell, triggering a wide range of cellular signaling events...

  11. Inflammation, immunity, and vaccines for Helicobacter pylori

    DEFF Research Database (Denmark)

    D'Elios, Mario M; Andersen, Leif P

    2009-01-01

    Helicobacter pylori infects almost half of the population worldwide and represents the major cause of gastroduodenal diseases, such as duodenal and gastric ulcer, gastric adenocarcinoma, autoimmune gastritis, and B-cell lymphoma of mucosa-associated lymphoid tissue. Helicobacter pylori induces th...... vaccine for H. pylori that will represent a novel and very important bullet against both infection and gastric cancer....

  12. Endosome–mitochondria juxtaposition during apoptosis induced by H. pylori VacA

    Science.gov (United States)

    Calore, F; Genisset, C; Casellato, A; Rossato, M; Codolo, G; Esposti, MD; Scorrano, L; de Bernard, M

    2011-01-01

    The vacuolating cytotoxin (VacA) is an important virulence factor of Helicobacter pylori with pleiotropic effects on mammalian cells, including the ability to trigger mitochondria-dependent apoptosis. However, the mechanism by which VacA exerts its apoptotic function is unclear. Using a genetic approach, in this study we show that killing by VacA requires the proapoptotic Bcl-2 family members BAX and BAK at the mitochondrial level, but not adequate endoplasmic reticulum Ca2+ levels, similarly controlled by BAX and BAK. A combination of subcellular fractionation and imaging shows that wild-type VacA, but not mutants in its channel-forming region, induces the accumulation of BAX on endosomes and endosome–mitochondria juxtaposition that precedes the retrieval of active BAX on mitochondria. It is noteworthy that in Bax- and Bak-deficient cells, VacA is unable to cause endosome–mitochondria juxtaposition and is not retrieved in mitochondria. Thus, VacA causes BAX/BAK-dependent juxtaposition of endosomes and mitochondria early in the process of cell death, revealing a new function for these proapoptotic proteins in the regulation of relative position of organelles. PMID:20431599

  13. Helicobacter pylori CagA causes mitotic impairment and induces chromosomal instability.

    Science.gov (United States)

    Umeda, Mayumi; Murata-Kamiya, Naoko; Saito, Yasuhiro; Ohba, Yusuke; Takahashi, Masayuki; Hatakeyama, Masanori

    2009-08-14

    Infection with cagA-positive Helicobacter pylori is the strongest risk factor for the development of gastric carcinoma. The cagA gene product CagA, which is delivered into gastric epithelial cells, specifically binds to and aberrantly activates SHP-2 oncoprotein. CagA also interacts with and inhibits partitioning-defective 1 (PAR1)/MARK kinase, which phosphorylates microtubule-associated proteins to destabilize microtubules and thereby causes epithelial polarity defects. In light of the notion that microtubules are not only required for polarity regulation but also essential for the formation of mitotic spindles, we hypothesized that CagA-mediated PAR1 inhibition also influences mitosis. Here, we investigated the effect of CagA on the progression of mitosis. In the presence of CagA, cells displayed a delay in the transition from prophase to metaphase. Furthermore, a fraction of the CagA-expressing cells showed spindle misorientation at the onset of anaphase, followed by chromosomal segregation with abnormal division axis. The effect of CagA on mitosis was abolished by elevated PAR1 expression. Conversely, inhibition of PAR1 kinase elicited mitotic delay similar to that induced by CagA. Thus, CagA-mediated inhibition of PAR1, which perturbs microtubule stability and thereby causes microtubule-based spindle dysfunction, is involved in the prophase/metaphase delay and subsequent spindle misorientation. Consequently, chronic exposure of cells to CagA induces chromosomal instability. Our findings reveal a bifunctional role of CagA as an oncoprotein: CagA elicits uncontrolled cell proliferation by aberrantly activating SHP-2 and at the same time induces chromosomal instability by perturbing the microtubule-based mitotic spindle. The dual function of CagA may cooperatively contribute to the progression of multistep gastric carcinogenesis.

  14. Helicobacter pylori and pancreatic diseases

    Institute of Scientific and Technical Information of China (English)

    Milutin; Bulajic; Nikola; Panic; Johannes; Matthias; L?hr

    2014-01-01

    A possible role for Helicobacter pylori(H. pylori) infec-tion in pancreatic diseases remains controversial. H. pylori infection with antral predomination leading to an increase in pancreatic bicarbonate output and induc-ing ductal epithelial cell proliferation could contribute to the development of pancreatic cancer via complex interactions with the ABO genotype, dietary and smok-ing habits and N-nitrosamine exposure of the host. Although the individual study data available so far is inconsistent, several meta-analyses have reported an increased risk for pancreatic cancer among H. pylori seropositive individuals. It has been suggested that H. pylori causes autoimmune pancreatitis due to molecu-lar mimicry between H. pylori a-carbonic anhydrase(a-CA) and human CA type Ⅱ, and between H. pylori plasminogen-binding protein and human ubiquitin-protein ligase E3 component n-recognin 2, enzymes that are highly expressed in the pancreatic ductal andacinar cells, respectively. Future studies involving large numbers of cases are needed in order to examine the role of H. pylori in autoimmune pancreatitis more fully. Considering the worldwide pancreatic cancer burden, as well as the association between autoimmune pan-creatitis and other autoimmune conditions, a complete elucidation of the role played by H. pylori in the gen-esis of such conditions could have a substantial impact on healthcare.

  15. Epigenetic silencing of miR-124 prevents spermine oxidase regulation: implications for Helicobacter pylori-induced gastric cancer.

    Science.gov (United States)

    Murray-Stewart, T; Sierra, J C; Piazuelo, M B; Mera, R M; Chaturvedi, R; Bravo, L E; Correa, P; Schneider, B G; Wilson, K T; Casero, R A

    2016-10-20

    Chronic inflammation contributes to the development of various forms of cancer. The polyamine catabolic enzyme spermine oxidase (SMOX) is induced in chronic inflammatory conditions, including Helicobacter pylori-associated gastritis, where its production of hydrogen peroxide contributes to DNA damage and subsequent tumorigenesis. MicroRNA expression levels are also altered in inflammatory conditions; specifically, the tumor suppressor miR-124 becomes silenced by DNA methylation. We sought to determine if this repression of miR-124 is associated with elevated SMOX activity and concluded that miR-124 is indeed a negative regulator of SMOX. In gastric adenocarcinoma cells harboring highly methylated and silenced mir-124 gene loci, 5-azacytidine treatment allowed miR-124 re-expression and decreased SMOX expression. Overexpression of an exogenous miR-124-3p mimic repressed SMOX mRNA and protein expression as well as H2O2 production by >50% within 24 h. Reporter assays indicated that direct interaction of miR-124 with the 3'-untranslated region of SMOX mRNA contributes to this negative regulation. Importantly, overexpression of miR-124 before infection with H. pylori prevented the induction of SMOX believed to contribute to inflammation-associated tumorigenesis. Compelling human in vivo data from H. pylori-positive gastritis tissues indicated that the mir-124 gene loci are more heavily methylated in a Colombian population characterized by elevated SMOX expression and a high risk for gastric cancer. Furthermore, the degree of mir-124 methylation significantly correlated with SMOX expression throughout the population. These results indicate a protective role for miR-124 through the inhibition of SMOX-mediated DNA damage in the etiology of H. pylori-associated gastric cancer.

  16. Rebamipide attenuates Helicobacter pylori CagA-induced self-renewal capacity via modulation of β-catenin signaling axis in gastric cancer-initiating cells.

    Science.gov (United States)

    Kang, Dong Woo; Noh, Yu Na; Hwang, Won Chan; Choi, Kang-Yell; Min, Do Sik

    2016-08-01

    Rebamipide, a mucosal-protective agent, is used clinically for treatment of gastritis and peptic ulcers induced by Helicobacter pylori (H. pylori) which is associated with increased risk of gastric cancer. Although rebamipide is known to inhibit the growth of gastric cancer cells, the action mechanisms of rebamipide in gastric carcinogenesis remains elusive. Here, we show that rebamipide suppresses H. pylori CagA-induced β-catenin and its target cancer-initiating cells (C-IC) marker gene expression via upregulation of miRNA-320a and -4496. Rebamipide attenuated in vitro self-renewal capacity of H. pylori CagA-infected gastric C-IC via modulation of miRNA-320a/-4496-β-catenin signaling axis. Moreover, rebamipide enhanced sensitivity to chemotherapeutic drugs in CagA-expressed gastric C-IC. Furthermore, rebamipide suppressed tumor-initiating capacity of gastric C-IC, probably via suppression of CagA-induced C-IC properties. These data provide novel insights for the efficacy of rebamipide as a chemoprotective drug against H. pylori CagA-induced carcinogenic potential. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Virulence of water-induced coccoid Helicobacter pylori and its experimental infection in mice

    Institute of Scientific and Technical Information of China (English)

    Fei-Fei She; Jian-Yin Lin; Jun-Yan Liu; Cheng Huang; Dong-Hui Su

    2003-01-01

    AIM: To explore the virulence and the infectivity of coccoid Helicobacter ppylori(H.pylori) transformed from spiral form by exposure to sterile tap water.METHODS: Three strains of H.pylori, isolated from gastric biopsy specimens of confirmed peptic ulcer, were converted from spiral into coccoid form by exposure to sterile tap water.Both spiral and coccoid forms of H.pylori were tested for the urease activity, and the adherence to Hep-2 cells. The presence of flagella was examined under electron microscopy. In the experimental animal infection, the spiral and coccoid forms of H.pylori originated from the same strain F49 were inoculated intragastrically into BALB/c mice respectively four times at a 3-day interval. Half of the mice from each group were sacrificed at Day 21 and Day 28 after the last inoculation. Histology and H.pylori colonization were detected by urease test of gastric mucosa, cultures of H. pylori,and electron microscopy and so on.RESULTS: The urease activity and the ability of adherence to Hep-2 cells were found to be lower in coccoid H.pylori than that in its spiral form. For example, the transformation in strain F44 led to a significant decrease of the adherence rate and adherence index from 70.0±5.3 % to 30.2±3.5 %(P<0.01), and from 2.6±0.4 to 0.86±0.3 (P<0.01),respectively. The flagella of coccoid H.pylori were observed under electron microscope. In the experimental infection in mice, the positive rate of gastric mucosa urease test was 93.8 % (15/16) in the group infected by spiral H.pylori and 50 % (8/16) in the group infected by coccoid H. pylori,and the estimated coccoid H.pylori colony number was 1.75 vs0,56. The positive rates of H. pyloriculture were 87.5 %(14/16) in spiral H. pylori group and 68.8 % (11/16) in coccoid H.pylorigroup. There was no significant difference in either urease test or bacterial culture rate between the groups examined at Day 21 and Day 28 after inoculation. Electron microscopic examination of the samples

  18. NF-κB and ERK-signaling pathways contribute to the gene expression induced by cag PAI-positive- Helicobacter pylori infection

    Institute of Scientific and Technical Information of China (English)

    Wataru Shibata; Yuzo Mitsuno; Naohiko Seki; Takao Kawabe; Masao Omata; Yoshihiro Hirata; Haruhiko Yoshida; Motoyuki Otsuka; Yujin Hoshida; Keiji Ogura; Shin Maeda; Tomoya Ohmae; Ayako Yanai

    2005-01-01

    AIM: To elucidate the sequential gene expression profile in AGS cells co-cultured with wild-type Helicobacter pylori(H pylori) as a model of H pylori-infected gastric epithelium,and to further examine the contribution of cag-pathogenicity islands (cagPAI)-coding type Ⅳ secretion system and the two pathways, nuclear factor kappa B (NF-κB) and extracellular signal-regulated kinases (ERK) on wild-type H pylori-induced gene expression.METHODS: Gene expression profiles induced by H pylori were evaluated in AGS gastric epithelial cells using cDNA microarray, which were present in the 4 600 independent clones picked up from the human gastric tissue. We also analyzed the contribution of NF-κB and ERK signaling on H pylori-induced gene expression by using inhibitors of specific signal pathways. The isogenic mutant with disrupted cagE (△cagE) was used to elucidate the role of cagPAI-encoding type Ⅳ secretion system in the gene expression profile.RESULTS: According to the expression profile, the genes were classified into four clusters. Among them, the clusters characterized by continuous upregulation were most conspicuous, and it contained many signal transducer activity-associated genes. The role of cagPAI on cultured cells was also investigated using isogenic mutant cagE,which carries non-functional cagPAI. Then the upregulation of more than 80% of the induced genes (476/566) was found to depend on cagPAI. Signal transducer pathway through NF-κB or ERK are the major pathways which are known to be activated by cagPAI-positive H pylori. The role of these pathways in the whole signal activation by cagPAIpositive H pylori was analyzed. The specific inhibitors against NF-κB or ERK pathway blocked the activation of gene expression in 65% (367/566) or 76% (429/566) of the genes whose activation appealed to depend on cagPAI.CONCLUSION: These results suggest that more than half of the genes induced by cagPAI-positive H pylori depend on NF-κB and ERK signaling activation

  19. Gastritis crónica antral por Helicobacter pylori en la infancia Chronic antral gastritis induced by Helicobacter pylori in children

    Directory of Open Access Journals (Sweden)

    Martha M. Gámez Escalona

    2008-03-01

    Full Text Available INTRODUCCIÓN. La investigación tiene como objetivos conocer la frecuencia de infección por Helicobacter pylori en los niños con gastritis crónica antral, estimar las diferencias en el comportamiento histológico de esta entidad en los niños con infección por Helicobacter pylori y sin ella, e identificar la posible relación entre la edad y las características histológicas de la gastritis crónica antral por Helicobacter pylori. MÉTODO. Se tomó como universo de estudio la totalidad de biopsias gástricas procesadas en el Hospital Pediátrico Provincial de Holguín, entre enero de 1991 y diciembre del 2004. Se determinó una muestra de 192 niños con diagnóstico histológico de gastritis crónica antral. Las biopsias fueron reevaluadas para detectar infección por Helicobacter pylori y su densidad de colonización junto a la actividad y la gravedad de las lesiones de la gastritis. RESULTADOS. Se encontró infección por Helicobacter pylori en el 67,7 % de los pacientes. Las formas activas predominaron en los casos con infección por Helicobacter pylori (116/130 a diferencia de quienes no tenían infección (5/62. Se identificó una relación estadísticamente significativa (p INTRODUCTION. The objective of this investigation is to know the frequency of infection caused by Helicobacter pylori in children with chronic antral gastritis, to estimate the differences in the histological behavior of this entity in children with infection due to Helicobacter pylori and without it, and to identify the possible relation existing between age and the histgological characteristics of chronic antral gastritis caused by Helicobacter pylori. METHODS. All the gastric biopsies processed in the Provincial Pediatric Hospital of Holguin from January 1991 to December 2004 were included in the study group. A sample of 192 children with histological diagnosis of chronic antral gastritis was determined. The biopsies were reevaluated to detect Helicobacter

  20. Virulence and potential pathogenicity of coccoid Helicobacter pylori induced by antibiotics

    Institute of Scientific and Technical Information of China (English)

    Fei Fei She; Dong Hui Su; Jian Yin Lin; Lin Ying Zhou

    2001-01-01

    AIM To explore the virulence and the potential pathogenicity of coccoid Helicobacter pylori (H. pylori) transformed from spiral form by exposure to antibiotic.METHODS Three strains of H. pylori, isolated from gastric biopsy specimens of confirmed peptic ulcer, were converted from spiral into coccoid from by exposure to metronidazole.Both spiral and coccoid form of H. pylori were tested for the urease activity, the adherence to Hep-2 cells and the vacuolating cytotoxicity to Hela cells, and the differences of the protein were analysed by SDS-PAGE and Western blot,The mutation of the genes including ureA, ureB,hpaA; vacA and cagA, related with virulence,was detected by means of PCR and PCR-SSCP.RESULTS In the coccoid H. pylori, the urease activity, the adherence to Hep-2 cells and the vacuolating cytotoxicity to Hela cells alldecreased. In strain F44, the rate and index of adherence reduced from 70.0% ± 5.3% to 33% ±5.1% and from 2.6 ±0.4 to 0.96 ±0.3 (P<0.01),respectively. The invasion of coccoid H. pylori into Hep-2 cell could be seen under electronmicroscope. SDS-PAGE showed that the content of the protein with the molecular weight over Mr74 000 decreased, and the hybriditional signal in band Mr 125 000 weakened, while the band Mr 110000 and Mr63000 strengthened in coccoid H. pylori as shown in Western blot. The results of PCR were all positive, and PCR-SSCP indicated that there may exist the point mutation in gene hpaA or vacA.CONCLUSION The virulence and the proteins with molecular weight over Mr74 000 in coccoid H. pylori decrease, but no deletion exists in amplification fragments from ureA, ureB, hpaA,vacA and cagA genes, suggesting that coccoid H. pylori may have potential pathogenicity.

  1. Inflammatory cytokine and microRNA responses of primary human dendritic cells cultured with Helicobacter pylori strains.

    Directory of Open Access Journals (Sweden)

    Anaïs eHocès De La Guardia

    2013-08-01

    Full Text Available Primary human dendritic cells (DC were used to explore the inflammatory effectors, including cytokines and microRNAs, regulated by Helicobacter pylori. In a 48 h ex-vivo co-culture system, both H. pylori B38 and B45 strains activated human DCs and promoted a strong inflammatory response characterized by the early production of pro-inflammatory TNF and IL-6 cytokines, followed by IL-10, IL-1ß and IL-23 secretion. IL-23 was the only cytokine dependent on the cag pathogenicity island status of the bacterial strains. DC activation and cytokine production were accompanied by an early miR-146a upregulation followed by a strong miR-155 induction, which mainly controlled TNFα production. These results pave the way for further investigations into the nature of H. pylori antigens and the subsequently activated signaling pathways involved in the inflammatory response to H. pylori infection, the deregulation of which may likely contribute to gastric lymphomagenesis.

  2. Helicobacter pylori-induced Sonic Hedgehog expression is regulated by NFκB pathway activation: the use of a novel in vitro model to study epithelial response to infection.

    Science.gov (United States)

    Schumacher, Michael A; Feng, Rui; Aihara, Eitaro; Engevik, Amy C; Montrose, Marshall H; Ottemann, Karen M; Zavros, Yana

    2015-02-01

    Helicobacter pylori (H. pylori) infection leads to acute induction of Sonic Hedgehog (Shh) in the stomach that is associated with the initiation of gastritis. The mechanism by which H. pylori induces Shh is unknown. Shh is a target gene of transcription factor Nuclear Factor-κB (NFκB). We hypothesize that NFκB mediates H. pylori-induced Shh. To visualize Shh ligand expression in response to H. pylori infection in vivo, we used a mouse model that expresses Shh fused to green fluorescent protein (Shh::GFP mice) in place of wild-type Shh. In vitro, changes in Shh expression were measured in response to H. pylori infection using 3-dimensional epithelial cell cultures grown from whole dissociated gastric glands (organoids). Organoids were generated from stomachs collected from the fundic region of control and mice expressing a parietal cell-specific deletion of Shh (PC-Shh(KO) mice). Within 2 days of infection, H. pylori induced Shh expression within parietal cells of Shh::GFP mice. Organoids expressed all major gastric cell markers, including parietal cell marker H(+) ,K(+) -ATPase and Shh. H. pylori infection of gastric organoids induced Shh expression; a response that was blocked by inhibiting NFκB signaling and correlated with IκB degradation. H. pylori infection of PC-Shh(KO) mouse-derived organoids did not result in the induction of Shh expression. Gastric organoids allow for the study of the interaction between H. pylori and the differentiated gastric epithelium independent of the host immune response. H. pylori induces Shh expression from the parietal cells, a response mediated via activation of NFκB signaling. © 2014 John Wiley & Sons Ltd.

  3. α-Lipoic Acid Inhibits Helicobacter pylori-Induced Oncogene Expression and Hyperproliferation by Suppressing the Activation of NADPH Oxidase in Gastric Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Eunyoung Byun

    2014-01-01

    Full Text Available Hyperproliferation and oncogene expression are observed in the mucosa of Helicobacter pylori- (H. pylori- infected patients with gastritis or adenocarcinoma. Expression of oncogenes such as β-catenin and c-myc is related to oxidative stress. α-Lipoic acid (α-LA, a naturally occurring thiol compound, acts as an antioxidant and has an anticancer effect. The aim of this study is to investigate the effect of α-LA on H. pylori-induced hyperproliferation and oncogene expression in gastric epithelial AGS cells by determining cell proliferation (viable cell numbers, thymidine incorporation, levels of reactive oxygen species (ROS, NADPH oxidase activation (enzyme activity, subcellular levels of NADPH oxidase subunits, activation of redox-sensitive transcription factors (NF-κB, AP-1, expression of oncogenes (β-catenin, c-myc, and nuclear localization of β-catenin. Furthermore, we examined whether NADPH oxidase mediates oncogene expression and hyperproliferation in H. pylori-infected AGS cells using treatment of diphenyleneiodonium (DPI, an inhibitor of NADPH oxidase. As a result, α-LA inhibited the activation of NADPH oxidase and, thus, reduced ROS production, resulting in inhibition on activation of NF-κB and AP-1, induction of oncogenes, nuclear translocation of β-catenin, and hyperproliferation in H. pylori-infected AGS cells. DPI inhibited H. pylori-induced activation of NF-κB and AP-1, oncogene expression and hyperproliferation by reducing ROS levels in AGS cells. In conclusion, we propose that inhibiting NADPH oxidase by α-LA could prevent oncogene expression and hyperproliferation occurring in H. pylori-infected gastric epithelial cells.

  4. Persistent colonization of Helicobacter pylori in human gut induces gastroduodenal diseases

    Directory of Open Access Journals (Sweden)

    Animesh Sarker

    2014-12-01

    Full Text Available Helicobacter pylori are gut bacteria colonize in the epithelial cell lining of the stomach and persist there for long du­ration. Around two-thirds of the world’s populations are infected with H. pylori and cause more than 90 percent of ulcers. The development of persistent inflammation is the main cause of chronic gastritis that finally results in a severe consequence known as stomach cancer. Two major virulence factors cytotoxin-associated gene product (cagA and the vacuolating toxin (vacA are mostly investigated as their close association with gastric carcinoma. In this review, host im­munity against H. pylori infection and their evasion mechanism are intensely explored. It is the fact, that understanding pin point molecular mechanisms of any infection is critical to develop novel strategies to prevent pertinent diseases. .J Microbiol Infect Dis 2014; 4(4: 170-176

  5. Helicobacter pylori Induced Phosphatidylinositol-3-OH Kinase/mTOR Activation Increases Hypoxia Inducible Factor-1α to Promote Loss of Cyclin D1 and G0/G1 Cell Cycle Arrest in Human Gastric Cells

    Science.gov (United States)

    Canales, Jimena; Valenzuela, Manuel; Bravo, Jimena; Cerda-Opazo, Paulina; Jorquera, Carla; Toledo, Héctor; Bravo, Denisse; Quest, Andrew F. G.

    2017-01-01

    Helicobacter pylori (H. pylori) is a human gastric pathogen that has been linked to the development of several gastric pathologies, such as gastritis, peptic ulcer, and gastric cancer. In the gastric epithelium, the bacterium modifies many signaling pathways, resulting in contradictory responses that favor both proliferation and apoptosis. Consistent with such observations, H. pylori activates routes associated with cell cycle progression and cell cycle arrest. H. pylori infection also induces the hypoxia-induced factor HIF-1α, a transcription factor known to promote expression of genes that permit metabolic adaptation to the hypoxic environment in tumors and angiogenesis. Recently, however, also roles for HIF-1α in the repair of damaged DNA and inhibition of gene expression were described. Here, we investigated signaling pathways induced by H. pylori in gastric cells that favor HIF-1α expression and the consequences thereof in infected cells. Our results revealed that H. pylori promoted PI3K/mTOR-dependent HIF-1α induction, HIF-1α translocation to the nucleus, and activity as a transcription factor as evidenced using a reporter assay. Surprisingly, however, transcription of known HIF-1α effector genes evaluated by qPCR analysis, revealed either no change (LDHA and GAPDH), statistically insignificant increases SLC2A1 (GLUT-1) or greatly enhance transcription (VEGFA), but in an HIF-1α-independent manner, as quantified by PCR analysis in cells with shRNA-mediated silencing of HIF-1α. Instead, HIF-1α knockdown facilitated G1/S progression and increased Cyclin D1 protein half-life, via a post-translational pathway. Taken together, these findings link H. pylori-induced PI3K-mTOR activation to HIF-1α induced G0/G1 cell cycle arrest by a Cyclin D1-dependent mechanism. Thus, HIF-1α is identified here as a mediator between survival and cell cycle arrest signaling activated by H. pylori infection. PMID:28401064

  6. H. pylori-Induced DNA Strand Breaks Are Introduced by Nucleotide Excision Repair Endonucleases and Promote NF-κB Target Gene Expression

    Directory of Open Access Journals (Sweden)

    Mara L. Hartung

    2015-10-01

    Full Text Available The human bacterial pathogen Helicobacter pylori exhibits genotoxic properties that promote gastric carcinogenesis. H. pylori introduces DNA double strand breaks (DSBs in epithelial cells that trigger host cell DNA repair efforts. Here, we show that H. pylori-induced DSBs are repaired via error-prone, potentially mutagenic non-homologous end-joining. A genome-wide screen for factors contributing to DSB induction revealed a critical role for the H. pylori type IV secretion system (T4SS. Inhibition of transcription, as well as NF-κB/RelA-specific RNAi, abrogates DSB formation. DSB induction further requires β1-integrin signaling. DSBs are introduced by the nucleotide excision repair endonucleases XPF and XPG, which, together with RelA, are recruited to chromatin in a highly coordinated, T4SS-dependent manner. Interestingly, XPF/XPG-mediated DNA DSBs promote NF-κB target gene transactivation and host cell survival. In summary, H. pylori induces XPF/XPG-mediated DNA damage through activation of the T4SS/β1-integrin signaling axis, which promotes NF-κB target gene expression and host cell survival.

  7. Dual Roles of Helicobacter pylori NapA in Inducing and Combating Oxidative Stress▿

    OpenAIRE

    Wang, Ge; Hong, Yang; Olczak, Adriana; Maier, Susan E.; Maier, Robert J.

    2006-01-01

    Neutrophil-activating protein (NapA) has been well documented to play roles in human neutrophil recruitment and in stimulating host cell production of reactive oxygen intermediates (ROI). A separate role for NapA in combating oxidative stress within H. pylori was implied by studies of various H. pylori mutant strains. Here, physiological analysis of a napA strain was the approach used to assess the iron-sequestering and stress resistance roles of NapA, its role in preventing oxidative DNA dam...

  8. Gastric Metaplasia Induced by Helicobacter pylori Is Associated with Enhanced SOX9 Expression via Interleukin-1 Signaling.

    Science.gov (United States)

    Serizawa, Takako; Hirata, Yoshihiro; Hayakawa, Yoku; Suzuki, Nobumi; Sakitani, Kosuke; Hikiba, Yohko; Ihara, Sozaburo; Kinoshita, Hiroto; Nakagawa, Hayato; Tateishi, Keisuke; Koike, Kazuhiko

    2015-12-07

    Histopathological changes of the gastric mucosa after Helicobacter pylori infection, such as atrophy, metaplasia, and dysplasia, are considered to be precursors of gastric cancer, yet the mechanisms of histological progression are unknown. The aim of this study was to analyze the histopathological features of the gastric mucosa in mice infected with H. pylori strain PMSS1 in relation to gastric stem cell marker expression. C57BL/6J mice infected with PMSS1 were examined for histopathological changes, levels of proinflammatory cytokines, and expression of stem cell markers. Histopathological gastritis scores, such as atrophy and metaplasia, and levels of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β), were increased after PMSS1 infection. Expression levels of the cell proliferation and stem cell markers CD44 and SOX9 were also significantly increased in PMSS1-infected mice. Importantly, almost all metaplastic cells induced by PMSS1 infection expressed SOX9. When IL-1 receptor (IL-1R) knockout mice were infected with PMSS1, metaplastic changes and expression levels of stem cell markers were significantly decreased compared with those in wild-type (WT) mice. In conclusion, H. pylori infection induced the expression of cytokines and stem cell markers and histopathological metaplasia in the mouse gastric mucosa. SOX9 expression, in particular, was strongly associated with metaplastic changes, and these changes were dependent on IL-1 signaling. The results suggested the importance of SOX9 in gastric carcinogenesis. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  9. Mimotopes selected with a neutralizing antibody against urease B from Helicobacter pylori induce enzyme inhibitory antibodies in mice upon vaccination

    Directory of Open Access Journals (Sweden)

    Long Min

    2010-11-01

    Full Text Available Abstract Background Urease B is an important virulence factor that is required for Helicobacter pylori to colonise the gastric mucosa. Mouse monoclonal antibodies (mAbs that inhibit urease B enzymatic activity will be useful as vaccines for the prevention and treatment of H. pylori infection. Here, we produced murine mAbs against urease B that neutralize the enzyme's activity. We mapped their epitopes by phage display libraries and investigated the immunogenicity of the selected mimotopes in vivo. Results The urease B gene was obtained (GenBank accession No. DQ141576 and the recombinant pGEX-4T-1/UreaseB protein was expressed in Escherichia coli as a 92-kDa recombinant fusion protein with glutathione-S-transferase (GST. Five mAbs U001-U005 were produced by a hybridoma-based technique with urease B-GST as an immunogen. Only U001 could inhibit urease B enzymatic activity. Immunoscreening via phage display libraries revealed two different mimotopes of urease B protein; EXXXHDM from ph.D.12-library and EXXXHSM from ph.D.C7C that matched the urease B proteins at 347-353 aa. The antiserum induced by selected phage clones clearly recognised the urease B protein and inhibited its enzymatic activity, which indicated that the phagotope-induced immune responses were antigen specific. Conclusions The present work demonstrated that phage-displayed mimotopes were accessible to the mouse immune system and triggered a humoral response. The urease B mimotope could provide a novel and promising approach for the development of a vaccine for the diagnosis and treatment of H. pylori infection.

  10. Effect of the Vacuolation of Helicobacter Pylori

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Cytotoxic test in vitro combined with cytochemical stain, fluorescent stain, transmission electronmicrograph was used to study the vacuolated effect by helicobacter pylori (H.pylori) (Toxin+) and its pathological mechanism. 78.26 % patients with peptic ulcer associated with H.pylori was infected with H.pylori (Toxin+), while 42.86 % patients with gastritis was infected with H.pylori (Toxin+). It was positive in vacuole with acridine orange and acid phosphatase stain. Transmission electronmicrograph of vacuole revealed the presence of abounding membrane. There was a closed relationship between infection with H.pylori (Toxin+) and peptic ulcer disease. The vacuole induced by H.pylori (Toxin+) was autophagosome, which was pathological phenomenon induced by toxin.

  11. Helicobacter pylori induced gastric immunopathology is associated with distinct microbiota changes in the large intestines of long-term infected Mongolian gerbils.

    Directory of Open Access Journals (Sweden)

    Markus M Heimesaat

    Full Text Available BACKGROUND: Gastrointestinal (GI inflammation in mice and men are frequently accompanied by distinct changes of the GI microbiota composition at sites of inflammation. Helicobacter (H. pylori infection results in gastric immunopathology accompanied by colonization of stomachs with bacterial species, which are usually restricted to the lower intestine. Potential microbiota shifts distal to the inflammatory process following long-term H. pylori infection, however, have not been studied so far. METHODOLOGY/PRINCIPAL FINDINGS: For the first time, we investigated microbiota changes along the entire GI tract of Mongolian gerbils after 14 months of infection with H. pylori B8 wildtype (WT or its isogenic ΔcagY mutant (MUT strain which is defective in the type IV secretion system and thus unable to modulate specific host pathways. Comprehensive cultural analyses revealed that severe gastric diseases such as atrophic pangastritis and precancerous transformations were accompanied by elevated luminal loads of E. coli and enterococci in the caecum and together with Bacteroides/Prevotella spp. in the colon of H. pylori WT, but not MUT infected gerbils as compared to naïve animals. Strikingly, molecular analyses revealed that Akkermansia, an uncultivable species involved in mucus degradation, was exclusively abundant in large intestines of H. pylori WT, but not MUT infected nor naïve gerbils. CONCLUSION/SIGNIFICANCE: Taken together, long-term infection of Mongolian gerbils with a H. pylori WT strain displaying an intact type IV secretion system leads to distinct shifts of the microbiota composition in the distal uninflamed, but not proximal inflamed GI tract. Hence, H. pylori induced immunopathogenesis of the stomach, including hypochlorhydria and hypergastrinemia, might trigger large intestinal microbiota changes whereas the exact underlying mechanisms need to be further unraveled.

  12. Helicobacter pylori Induced Gastric Immunopathology Is Associated with Distinct Microbiota Changes in the Large Intestines of Long-Term Infected Mongolian Gerbils

    Science.gov (United States)

    Heimesaat, Markus M.; Fischer, André; Plickert, Rita; Wiedemann, Tobias; Loddenkemper, Christoph; Göbel, Ulf B.

    2014-01-01

    Background Gastrointestinal (GI) inflammation in mice and men are frequently accompanied by distinct changes of the GI microbiota composition at sites of inflammation. Helicobacter (H.) pylori infection results in gastric immunopathology accompanied by colonization of stomachs with bacterial species, which are usually restricted to the lower intestine. Potential microbiota shifts distal to the inflammatory process following long-term H. pylori infection, however, have not been studied so far. Methodology/Principal Findings For the first time, we investigated microbiota changes along the entire GI tract of Mongolian gerbils after 14 months of infection with H. pylori B8 wildtype (WT) or its isogenic ΔcagY mutant (MUT) strain which is defective in the type IV secretion system and thus unable to modulate specific host pathways. Comprehensive cultural analyses revealed that severe gastric diseases such as atrophic pangastritis and precancerous transformations were accompanied by elevated luminal loads of E. coli and enterococci in the caecum and together with Bacteroides/Prevotella spp. in the colon of H. pylori WT, but not MUT infected gerbils as compared to naïve animals. Strikingly, molecular analyses revealed that Akkermansia, an uncultivable species involved in mucus degradation, was exclusively abundant in large intestines of H. pylori WT, but not MUT infected nor naïve gerbils. Conclusion/Significance Taken together, long-term infection of Mongolian gerbils with a H. pylori WT strain displaying an intact type IV secretion system leads to distinct shifts of the microbiota composition in the distal uninflamed, but not proximal inflamed GI tract. Hence, H. pylori induced immunopathogenesis of the stomach, including hypochlorhydria and hypergastrinemia, might trigger large intestinal microbiota changes whereas the exact underlying mechanisms need to be further unraveled. PMID:24941045

  13. Helicobacter pylori induced gastric immunopathology is associated with distinct microbiota changes in the large intestines of long-term infected Mongolian gerbils.

    Science.gov (United States)

    Heimesaat, Markus M; Fischer, André; Plickert, Rita; Wiedemann, Tobias; Loddenkemper, Christoph; Göbel, Ulf B; Bereswill, Stefan; Rieder, Gabriele

    2014-01-01

    Gastrointestinal (GI) inflammation in mice and men are frequently accompanied by distinct changes of the GI microbiota composition at sites of inflammation. Helicobacter (H.) pylori infection results in gastric immunopathology accompanied by colonization of stomachs with bacterial species, which are usually restricted to the lower intestine. Potential microbiota shifts distal to the inflammatory process following long-term H. pylori infection, however, have not been studied so far. For the first time, we investigated microbiota changes along the entire GI tract of Mongolian gerbils after 14 months of infection with H. pylori B8 wildtype (WT) or its isogenic ΔcagY mutant (MUT) strain which is defective in the type IV secretion system and thus unable to modulate specific host pathways. Comprehensive cultural analyses revealed that severe gastric diseases such as atrophic pangastritis and precancerous transformations were accompanied by elevated luminal loads of E. coli and enterococci in the caecum and together with Bacteroides/Prevotella spp. in the colon of H. pylori WT, but not MUT infected gerbils as compared to naïve animals. Strikingly, molecular analyses revealed that Akkermansia, an uncultivable species involved in mucus degradation, was exclusively abundant in large intestines of H. pylori WT, but not MUT infected nor naïve gerbils. Taken together, long-term infection of Mongolian gerbils with a H. pylori WT strain displaying an intact type IV secretion system leads to distinct shifts of the microbiota composition in the distal uninflamed, but not proximal inflamed GI tract. Hence, H. pylori induced immunopathogenesis of the stomach, including hypochlorhydria and hypergastrinemia, might trigger large intestinal microbiota changes whereas the exact underlying mechanisms need to be further unraveled.

  14. Helicobacter pylori Outer Membrane Vesicle Proteins Induce Human Eosinophil Degranulation via a β2 Integrin CD11/CD18- and ICAM-1-Dependent Mechanism

    Directory of Open Access Journals (Sweden)

    Su Hyuk Ko

    2015-01-01

    Full Text Available Eosinophil cationic protein (ECP, a cytotoxic protein contained in eosinophils granules, can contribute to various inflammatory responses. Although Helicobacter pylori infection increases infiltration of eosinophils, the mechanisms of eosinophil degranulation by H. pylori infection are largely unknown. The goal of this study was to investigate the role of H. pylori outer membrane vesicles (OMVs in modulating eosinophil degranulation. We found that eosinophils treated with H. pylori OMVs released significantly more ECP compared with untreated controls. In addition, eosinophils cocultured with OMV-preexposed primary gastric epithelial cells exhibited significantly increased ECP release. Similarly, eosinophils cocultured with culture supernatant (CM from primary gastric epithelial cells exposed to OMVs (OMV-CM released significantly higher amounts of ECP compared with eosinophils cocultured with CM from unexposed control cells. Furthermore, OMVs and OMV-CM both induced the upregulation of ICAM-1 on gastric epithelial cells and β2 integrin CD11b on eosinophils. In addition, both transduction of ICAM-1 shRNA into gastric epithelial cells and treatment with neutralizing mAbs to CD18 significantly decreased OMV-mediated or OMV-CM-mediated release of ECP. These results suggest that the eosinophil degranulation response to H. pylori OMVs occurs via a mechanism that is dependent on both β2 integrin CD11/CD18 and ICAM-1.

  15. Helicobacter pylori outer membrane vesicle proteins induce human eosinophil degranulation via a β2 Integrin CD11/CD18- and ICAM-1-dependent mechanism.

    Science.gov (United States)

    Ko, Su Hyuk; Jeon, Jong Ik; Kim, Young-Jeon; Yoon, Ho Joo; Kim, Hyeyoung; Kim, Nayoung; Kim, Joo Sung; Kim, Jung Mogg

    2015-01-01

    Eosinophil cationic protein (ECP), a cytotoxic protein contained in eosinophils granules, can contribute to various inflammatory responses. Although Helicobacter pylori infection increases infiltration of eosinophils, the mechanisms of eosinophil degranulation by H. pylori infection are largely unknown. The goal of this study was to investigate the role of H. pylori outer membrane vesicles (OMVs) in modulating eosinophil degranulation. We found that eosinophils treated with H. pylori OMVs released significantly more ECP compared with untreated controls. In addition, eosinophils cocultured with OMV-preexposed primary gastric epithelial cells exhibited significantly increased ECP release. Similarly, eosinophils cocultured with culture supernatant (CM) from primary gastric epithelial cells exposed to OMVs (OMV-CM) released significantly higher amounts of ECP compared with eosinophils cocultured with CM from unexposed control cells. Furthermore, OMVs and OMV-CM both induced the upregulation of ICAM-1 on gastric epithelial cells and β2 integrin CD11b on eosinophils. In addition, both transduction of ICAM-1 shRNA into gastric epithelial cells and treatment with neutralizing mAbs to CD18 significantly decreased OMV-mediated or OMV-CM-mediated release of ECP. These results suggest that the eosinophil degranulation response to H. pylori OMVs occurs via a mechanism that is dependent on both β2 integrin CD11/CD18 and ICAM-1.

  16. Helicobacter pylori vesicles carrying CagA localize in the vicinity of cell-cell contacts and induce histone H1 binding to ATP in epithelial cells.

    Science.gov (United States)

    Turkina, Maria V; Olofsson, Annelie; Magnusson, Karl-Eric; Arnqvist, Anna; Vikström, Elena

    2015-06-01

    Helicobacter pylori produces outer membrane vesicles (OMV), delivering bacterial substances including the oncogenic cytotoxin-associated CagA protein to their surroundings. We investigated the effects of H. pylori OMV carrying CagA (OMV-CagA) on cell junctions and ATP-binding proteome of epithelial monolayers, using proteomics, mass spectrometry and imaging. OMV-CagA localized in close vicinity of ZO-1 tight junction protein and induced histone H1 binding to ATP. We suggest the expression of novel events in the interactions between H. pylori OMV and epithelia, which may have an influence on host gene transcription and lead to different outcomes of an infection and development of cancer. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Helicobacter pylori

    OpenAIRE

    BATESON, M

    2000-01-01

    Helicobacter pylori infection is a major cause of peptic ulcer disease, and its detection and eradication are now an important part of gastroenterology. Effective regimes are available which will eliminate the organism in about 90% of cases in developed countries.


Keywords: Helicobacter pylori

  18. Helicobacter pylori and Nonmalignant Diseases.

    Science.gov (United States)

    Potamitis, Georgios S; Axon, Anthony T R

    2015-09-01

    Helicobacter pylori is responsible for most peptic ulcers, plays a role in functional dyspepsia and is thought by some to influence the course of gastroesophageal reflux disease. This article addresses recent studies that have been published in connection with these diseases. H. pylori-associated peptic ulcer is declining in prevalence but the incidence of perforation and bleeding remains high especially in the elderly. All H. pylori associated peptic ulcers should be treated by eradication of the infection. Dyspepsia is a common disorder that affects up to 25% of the population. About 8% of cases that are infected with H. pylori will respond to treatment of the infection. The association between H. pylori and gastroesophageal reflux disease continues to be debated, a number of studies have shown that there is a negative association between H. pylori infection and Gastroesophageal reflux disease but treatment of H. pylori has not been shown to induce reflux or to affect the response to medication. Gastric atrophy is known to extend when acid suppression is used in infected patients implying that H. pylori treatment should be used in infected patients who are to undergo long-term Proton Pump Inhibitor therapy.

  19. Study of miR-125b, miR-29a and miR-155-5p as biomarkers of tuberculous meningitis%miR-125b、miR-29a和miR-155-5p作为诊断结核性脑膜炎生物标志的研究

    Institute of Scientific and Technical Information of China (English)

    柴璐璐; 田宋新; 袁俐; 王宏

    2015-01-01

    Objective To investigate the expression levels of microRNA(miR)-125b, miR-29a and miR-155-5p in ce⁃rebrospinal fluid (CSF) and plasma from the patients with tuberculous meningitis and their clinic significance. Methods Cerebrospinal fluid and plasma samples were collected from 20 patients with tuberculous meningitis (tuberculous meningitis group) and 20 patients suffered from primary headache (control group). The total RNAs were extracted.The levels of miR-125b, miR-29a and miR-155-5p were determined by real-time quantitative PCR (q-PCR). Results Levels of miR-29a and miR-125b in both CSF and plasma of patients in tuberculous meningitis group were significantly higher than those in pa⁃tients from control group with statistical significance (P<0.01). Mean time, the level of miR-155-5p in plasma but not in CSF of patients in tuberculous meningitis group was higher than those in control group with statistical significance ( P<0.01). Conclusion Expression of miR-125b, miR-29a and miR-155-5p may participate in regulating the occurrence and development of tuberculous meningitis. And miR-125b and miR-29a may be used as potential biomarkers for diagnosing tu⁃berculous meningitis.%目的:探讨结核性脑膜炎患者脑脊液及血浆中microRNA (miR)-125b、miR-29a和miR-155-5p的表达水平及其临床意义。方法收集20例结核性脑膜炎患者(结脑组)和20例原发性头痛患者(对照组)的脑脊液和血浆,分别提取总RNA,使用实时定量PCR方法分别检测脑脊液和血浆中miR-125b、miR-29a及miR-155-5p的表达水平。结果与对照组相比,结脑组脑脊液、血浆中miR-29a、miR-125b表达水平明显上调,结脑组血浆中miR-155-5p表达水平明显上调,差异均有统计学意义(均P<0.01),而2组脑脊液中miR-155-5p表达水平比较差异无统计学意义。结论 miR-125b、miR-29a和miR-155-5p可能参与了调节结核性脑膜炎的发生、发展过程,miR-125b和miR-29a有可能作为潜在的诊断结核性脑膜炎的生物学标志。

  20. Epigenetic regulation of DNA repair machinery in Helicobacter pylori-induced gastric carcinogenesis.

    Science.gov (United States)

    Santos, Juliana Carvalho; Ribeiro, Marcelo Lima

    2015-08-14

    Although thousands of DNA damaging events occur in each cell every day, efficient DNA repair pathways have evolved to counteract them. The DNA repair machinery plays a key role in maintaining genomic stability by avoiding the maintenance of mutations. The DNA repair enzymes continuously monitor the chromosomes to correct any damage that is caused by exogenous and endogenous mutagens. If DNA damage in proliferating cells is not repaired because of an inadequate expression of DNA repair genes, it might increase the risk of cancer. In addition to mutations, which can be either inherited or somatically acquired, epigenetic silencing of DNA repair genes has been associated with carcinogenesis. Gastric cancer represents the second highest cause of cancer mortality worldwide. The disease develops from the accumulation of several genetic and epigenetic changes during the lifetime. Among the risk factors, Helicobacter pylori (H. pylori) infection is considered the main driving factor to gastric cancer development. Thus, in this review, we summarize the current knowledge of the role of H. pylori infection on the epigenetic regulation of DNA repair machinery in gastric carcinogenesis.

  1. IL-17a and IL-22 Induce Expression of Antimicrobials in Gastrointestinal Epithelial Cells and May Contribute to Epithelial Cell Defense against Helicobacter pylori.

    Directory of Open Access Journals (Sweden)

    Beverly R E A Dixon

    Full Text Available Helicobacter pylori colonization of the human stomach can lead to adverse clinical outcomes including gastritis, peptic ulcers, or gastric cancer. Current data suggest that in addition to bacterial virulence factors, the magnitude and types of immune responses influence the outcome of colonization. Specifically, CD4+ T cell responses impact the pathology elicited in response to H. pylori. Because gastritis is believed to be the initiating host response to more detrimental pathological outcomes, there has been a significant interest in pro-inflammatory T cell cytokines, including the cytokines produced by T helper 17 cells. Th17 cells produce IL-17A, IL-17F, IL-21 and IL-22. While these cytokines have been linked to inflammation, IL-17A and IL-22 are also associated with anti-microbial responses and control of bacterial colonization. The goal of this research was to determine the role of IL-22 in activation of antimicrobial responses in models of H. pylori infection using human gastric epithelial cell lines and the mouse model of H. pylori infection. Our data indicate that IL-17A and IL-22 work synergistically to induce antimicrobials and chemokines such as IL-8, components of calprotectin (CP, lipocalin (LCN and some β-defensins in both human and primary mouse gastric epithelial cells (GEC and gastroids. Moreover, IL-22 and IL-17A-activated GECs were capable of inhibiting growth of H. pylori in vitro. While antimicrobials were activated by IL-17A and IL-22 in vitro, using a mouse model of H. pylori infection, the data herein indicate that IL-22 deficiency alone does not render mice more susceptible to infection, change their antimicrobial gene transcription, or significantly change their inflammatory response.

  2. HELICOBACTER PYLORI

    Science.gov (United States)

    Helicobacter pylori is a pathogenic bacteria which inhabits the human stomach and upper gastrointestinal tract. This encyclopedic entry summarizes the potential role of this organism as a waterborne pathogen. Information is provided on the physiology and morphology of this bacter...

  3. HELICOBACTER PYLORI

    Science.gov (United States)

    Helicobacter pylori is a pathogenic bacteria which inhabits the human stomach and upper gastrointestinal tract. This encyclopedic entry summarizes the potential role of this organism as a waterborne pathogen. Information is provided on the physiology and morphology of this bacter...

  4. [Helicobacter pylori and Arteriosclerosis].

    Science.gov (United States)

    Matsui, Teruaki

    2011-03-01

    Helicobacter pylori (H. pylori) infection-related diseases are known to include gastritis, gastric and duodenal ulcer, gastric cancer, gastric MALT lymphoma, idiopathic thrombocytopenic purpura, iron-deficient anemia, urticaria, reflux esophagitis, and some lifestyle-related diseases. It is indicated that homocysteine involved with arteriosclerosis induces lifestyle-related diseases. Homocysteine is decomposed to methionine and cysteine (useful substances) in the liver, through the involvement of vitamin B₁₂ (VB₁₂) and folic acid. However, deficiency of VB₁₂ and folic acid induces an increase in unmetabolized homocysteine stimulating active oxygen and promoting arteriosclerosis. VB₁₂ and folic acid are activated by the intrinsic factors of gastric parietal cells and gastric acid. The question of whether homocysteine, as a trigger of arteriosclerosis, was influenced by H. pylori infection was investigated. H. pylori infection induces atrophy of the gastric mucosa, and the function of parietal cells decreases with the atrophy to inactivate its intrinsic factor. The inactivation of the intrinsic factor causes a deficiency of VB₁₂ and folic acid to increase homocysteine's chances of triggering arteriosclerosis. The significance and usefulness of H. pylori eradication therapy was evaluated for its ability to prevent arteriosclerosis that induces lifestyle-related diseases. Persons with positive and negative results of H. pylori infection were divided into a group of those aged 65 years or more (early and late elderly) and a group of those under 65 years of age, and assessed for gastric juice. For twenty-five persons from each group who underwent gastrointestinal endoscopy, the degree of atrophy of the gastric mucosa was observed. Blood homocysteine was measured as a novel index of arteriosclerosis, as well as VB₁₂ and folic acid that affect the metabolism of homocysteine, and then activated by gastric acid and intrinsic factors. Their

  5. Colchicine-clarithromycin-induced rhabdomyolysis in Familial Mediterranean Fever patients under treatment for Helicobacter pylori.

    Science.gov (United States)

    Cohen, Oren; Locketz, Garrett; Hershko, Alon Y; Gorshtein, Alexander; Levy, Yair

    2015-11-01

    Chronic administration of colchicine remains a mainstay of therapy for patients with Familial Mediterranean Fever (FMF). As this medication is a strong CYP3A4 inhibitor, it has the potential to interact with many routinely used medications. One such medication is clarithromycin, itself a strong inhibitor of the same enzyme, and a typical choice for triple therapy eradication of H. pylori. Various sequelae of colchicine-clarithromycin interaction have been documented and can be expected by prescribing physicians, with rhabdomyolysis, though rare, being among the most serious. Review of cases from a tertiary academic medical center and full PubMed/MEDLINE literature review. Despite the prevalence of diseases treated with clarithromycin and the expected drug interaction with colchicine, only two cases in the literature document clinical rhabdomyolysis due to colchicine-clarithromycin interaction. In neither case, however, were patients undergoing treatment for FMF. Herein, we describe the first two cases in the literature of clinical rhabdomyolysis in FMF patients under colchicine therapy after administration of clarithromycin as part of therapy treating H. pylori infection.

  6. 淋巴瘤患者血浆中miR-21、miR-155、miR-210的表达及临床意义%Expressions of miR-21, miR-155 and miR-210 in Plasma of Patients with Lymphoma and Its Clinical Significance

    Institute of Scientific and Technical Information of China (English)

    葛甜甜; 宋嘉; 王化泉; 邢莉民; 关晶; 李丽娟; 邵宗鸿; 梁勇; 付蓉; 王国锦; 阮二宝; 瞿文; 王晓明; 刘鸿; 吴玉红

    2012-01-01

    This study was purposed to investigate the expressions of miR-21, miR-155 and miR-210 in plasma of patients with lymphoma, and explore their role played in diagnosis, evaluation of chemotherapy effect and prognosis of lymphoma. The expressions of miR-21, miR-155 and miR-210 were assayed by RT-PCR in plasma of 54 cases of lymphoma, 10 cases of lymphonode inflammation and 27 cases of normal controls. The results indicated that the expressions of miR-21, miR-155 and miR-210 in plasma of lymphoma patients were higher than those of control group and lymphonode inflammation group(P 0.05). The expression of miR-21 in plasma of lymphoma patient group significantly correlated with their serum LDH level. The expressions of miR-21 and miR-210 in plasma of previously untreated lymphoma patient group were higher than those of the patients treated for 6 or more courses (P < 0.05). The diagnostic accuracy of miR-21, miR-155 and miR-210 used for lymphoma patients was 56% , 65% , 48% respectively, and reached to 83% when combined three of them. It is concluded that the expressions of miR-21 , miR-155 and miR-210 in plasma of lymphoma patients were significantly higher. Detection of these 3 miRNA in plasma of patients can contribute to the clinical diagnosis, treatment and prognosis evaluation of lymphoma.%本研究旨在检测淋巴瘤患者血浆中miR-21、miR-155、miR-210的表达,分析其与临床特征的相关性并探讨其在淋巴瘤诊断、评价疗效及预后方面的作用.运用RT-PCR方法检测淋巴瘤患者(55例)、淋巴结炎性肿大患者(10例)和正常对照(27名)血浆中miR-21、miR-155、miR-210的表达.结果表明,淋巴瘤患者血浆中miR-21、miR-155、miR-210的表达量均明显高于正常对照及淋巴结炎性肿大患者(P<0.05),淋巴结炎性肿大患者血浆中miR-21、miR-210的表达量与正常对照无显著差异.淋巴瘤患者血浆中miR-21的表达随血清乳酸脱氢酶水平增高而增高.初治淋巴瘤患者血浆中miR-21、miR-210的表达量明显高于6个疗程以上患者的表达量(P<0.05).miR-21、miR-155、miR-210用于淋巴瘤的诊断准确度分别可达56.4%、65.3%、47.6%,三者联合诊断率可达82.7%.结论:淋巴瘤血浆中miR-21、miR-155、miR-210的表达量增高,检测三者在血浆中的表达量有助于临床淋巴瘤的诊断及疗效、预后的判断.

  7. Helicobacter pylori infection generates genetic instability in gastric cells

    DEFF Research Database (Denmark)

    Machado, Ana Manuel; Figueiredo, C.; Seruca, R.

    2010-01-01

    The discovery that Helicobacter pylori is associated with gastric cancer has led to numerous studies that investigate the mechanisms by which H. pylori induces carcinogenesis. Gastric cancer shows genetic instability both in nuclear and mitochondrial DNA, besides impairment of important DNA repair...... of the host, such as oxidative damage, methylation, chromosomal instability, microsatellite instability, and mutations. Interestingly, H. pylori infection generates genetic instability in nuclear and mitochondrial DNA. Based on the reviewed literature we conclude that H. pylori infection promotes gastric...

  8. Helicobacter pylori Test

    Science.gov (United States)

    ... urease test (RUT) for H. pylori Formal name: Helicobacter pylori Related tests: Gastrin At a Glance Test Sample ... else I should know? How is it used? Helicobacter pylori testing is used to diagnose an infection due ...

  9. Regulation of the actin cytoskeleton in Helicobacter pylori-induced migration and invasive growth of gastric epithelial cells

    Directory of Open Access Journals (Sweden)

    Rieder Gabriele

    2011-11-01

    Full Text Available Abstract Dynamic rearrangement of the actin cytoskeleton is a significant hallmark of Helicobacter pylori (H. pylori infected gastric epithelial cells leading to cell migration and invasive growth. Considering the cellular mechanisms, the type IV secretion system (T4SS and the effector protein cytotoxin-associated gene A (CagA of H. pylori are well-studied initiators of distinct signal transduction pathways in host cells targeting kinases, adaptor proteins, GTPases, actin binding and other proteins involved in the regulation of the actin lattice. In this review, we summarize recent findings of how H. pylori functionally interacts with the complex signaling network that controls the actin cytoskeleton of motile and invasive gastric epithelial cells.

  10. Helicobacter pylori infection generates genetic instability in gastric cells

    DEFF Research Database (Denmark)

    Machado, Ana Manuel; Figueiredo, C.; Seruca, R.

    2010-01-01

    The discovery that Helicobacter pylori is associated with gastric cancer has led to numerous studies that investigate the mechanisms by which H. pylori induces carcinogenesis. Gastric cancer shows genetic instability both in nuclear and mitochondrial DNA, besides impairment of important DNA repair...... pathways. As such, this review highlights the consequences of H. pylori infection on the integrity of DNA in the host cells. By down-regulating major DNA repair pathways, H. pylori infection has the potential to generate mutations. In addition, H. pylori infection can induce direct changes on the DNA...... of the host, such as oxidative damage, methylation, chromosomal instability, microsatellite instability, and mutations. Interestingly, H. pylori infection generates genetic instability in nuclear and mitochondrial DNA. Based on the reviewed literature we conclude that H. pylori infection promotes gastric...

  11. Helicobacter pylori and non-malignant diseases.

    Science.gov (United States)

    Furuta, Takahisa; Delchier, Jean-Charles

    2009-09-01

    It is well known that Helicobacter pylori infection is associated with many nonmalignant disorders such as gastritis, peptic ulcer, gastroesophageal reflux disease (GERD), gastric polyp, nonsteroidal anti-inflammatory drug (NSAID)/aspirin-induced gastric injury, and functional dyspepsia. In 2008, interesting articles on the association of H. pylori infection with these disorders were presented, some of which intended to reveal the mechanisms of inter-individual differences in response to H. pylori infection, and have demonstrated that genetic differences in host and bacterial factors as well as environmental factors account for these differences. A decline in the occurrence of peptic ulcer related to H. pylori was confirmed. An inverse relationship between H. pylori infection and GERD was also confirmed but the impact of gastric atrophy on the prevention of GERD remained debatable. For NSAID-induced gastric injury, eradication of H. pylori infection has been recommended. During this year, eradication of H. pylori infection was recommended for patients treated with antiplatelet therapy as well as aspirin and NSAID. It was also reported that for patients with functional dyspepsia, eradication of H. pylori offers a modest but significant benefit.

  12. Innate immune responses to Helicobacter pylori infection: an overview.

    Science.gov (United States)

    Patel, Milan K; Trombly, Melanie I; Kurt-Jones, Evelyn A

    2012-01-01

    Innate immune receptors detect Helicobacter pylori infection and trigger downstream signaling events that result in the production of cytokines and interferon-β. This chapter gives an overview of the receptors and their roles in responding to H. pylori infection and details the downstream signaling events. The tools that have been developed to study the innate immune response to H. pylori are also discussed. Understanding the immune response to H. pylori is critical to develop better treatments for H. pylori-induced disease states including gastric malignancies and cancer.

  13. BH3-only protein Bim is associated with the degree of Helicobacter pylori-induced gastritis and is localized to the mitochondria of inflammatory cells in the gastric mucosa.

    Science.gov (United States)

    Akazawa, Yuko; Matsuda, Katsuya; Isomoto, Hajime; Matsushima, Kayoko; Kido, Yoko; Urabe, Shigetoshi; Yamaghchi, Naoyuki; Ohnita, Ken; Takeshima, Fuminao; Kondo, Hisayoshi; Tsugawa, Hitoshi; Suzuki, Hidekazu; Moss, Joel; Nakao, Kazuhiko; Nakashima, Masahiro

    2015-09-01

    BH3-only protein, Bim, is a pro-apoptotic protein that mediates mitochondria-dependent cell death. However, the role of Bim in Helicobacter pylori-associated gastritis remains unclear. This study aimed to assess the cellular localization of Bim and its possible role in H. pylori-induced gastritis. The study was conducted on biopsy specimens obtained from 80 patients who underwent upper gastrointestinal endoscopy (H. pylori-negative: n=30, positive: n=50). Association between Bim mRNA expression and severity of gastritis was evaluated and the localization of Bim was examined by immunofluorescence. Bim mRNA expression was positively correlated with the degree of gastritis, as defined by the Sydney system. Immunohistochemical analysis confirmed increased Bim expression in H. pylori-infected gastric mucosa compared with uninfected mucosa in both humans and mice. Bim localized in myeloperoxidase- and CD138-positive cells of H. pylori-infected lamina propria and submucosa of the gastric tract, indicating that this protein is predominantly expressed in neutrophils and plasma cells. In contrast, Bim did not localize in CD20-, CD3-, or CD68-positive cells. Bim was expressed in the mitochondria, where it was partially co-localized with activated Bax and cleaved-PARP. In conclusion, Bim is expressed in neutrophils and plasma cells in H. pylori-associated gastritis, where it may participate in the termination of inflammatory response by causing mitochondria-mediated apoptosis in specific leucocytes. Copyright © 2015 Elsevier GmbH. All rights reserved.

  14. New immunological investigations on Helicobacter pylori-induced gastric ulcer in patients.

    Science.gov (United States)

    Rahimi, Hamid Reza; Rasouli, Manoochehr; Jamshidzadeh, Akram; Farshad, Shohreh; Firoozi, Mehdi Saberi; Taghavi, Ali Reza; Kiany, Simin

    2013-06-01

    Although Helicobacter pylori (Hp) plays an important role in the pathogenesis of chronic gastritis and gastric ulcer, little is known about the probable mechanisms of these types of gastrointestinal damage. To determine the precise mechanisms involved in ulcer formation, immune responses in patients with gastric ulcer (GUP) caused by Hp infection (Hp(+)) were compared with those of other gastritis patients (GP). The sensitivity and proliferation of peripheral blood mononuclear cells (PBMNCs) obtained from patients were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against exposure with complex Hp crude antigen (HPCA) and mitogen (phytohemagglutinin, PHA). Production of inflammatory cytokines, including interleukin (IL)-1β and IL-8, in serum and supernatants of PBMNCs were then measured by ELISA. It was found that, after stimulation with PHA, both IL-8 and IL-1β concentrations in sera and supernatants as well as proliferation and sensitivity were statistically greater in GUP Hp(+) than GP Hp(-) . Furthermore, HPCA inhibited the proliferation of PBMNCs dose-dependently; however, it stimulated IL-8 and IL-1β production in supernatants of mononuclear cells. Therefore, the up-regulated concentrations of IL-8 and IL-1β may have been caused by increase in the size of mononuclear cell subpopulations or in their cytokine secretory activity, indicating the greatest cell responsiveness in GUP Hp(+) patients. These results suggest that tissue damage and ulcers occur in patients who produce more IL-8 and IL-1β than patients who do not develop ulcers; the former consequently have more activated immune cells at the site of infection. Therefore, both host responses and Hp virulence factors may be involved in the development of gastric ulcers.

  15. Regulation of RKIP function by Helicobacter pylori in gastric cancer.

    Directory of Open Access Journals (Sweden)

    Erika L Moen

    Full Text Available Helicobacter pylori (H. pylori is a gram-negative, spiral-shaped bacterium that infects more than half of the world's population and is a major cause of gastric adenocarcinoma. The mechanisms that link H. pylori infection to gastric carcinogenesis are not well understood. In the present study, we report that the Raf-kinase inhibitor protein (RKIP has a role in the induction of apoptosis by H. pylori in gastric epithelial cells. Western blot and luciferase transcription reporter assays demonstrate that the pathogenicity island of H. pylori rapidly phosphorylates RKIP, which then localizes to the nucleus where it activates its own transcription and induces apoptosis. Forced overexpression of RKIP enhances apoptosis in H. pylori-infected cells, whereas RKIP RNA inhibition suppresses the induction of apoptosis by H. pylori infection. While inducing the phosphorylation of RKIP, H. pylori simultaneously targets non-phosphorylated RKIP for proteasome-mediated degradation. The increase in RKIP transcription and phosphorylation is abrogated by mutating RKIP serine 153 to valine, demonstrating that regulation of RKIP activity by H. pylori is dependent upon RKIP's S153 residue. In addition, H. pylori infection increases the expression of Snail, a transcriptional repressor of RKIP. Our results suggest that H. pylori utilizes a tumor suppressor protein, RKIP, to promote apoptosis in gastric cancer cells.

  16. Helicobacter pylori, Cancer, and the Gastric Microbiota.

    Science.gov (United States)

    Wroblewski, Lydia E; Peek, Richard M

    Gastric adenocarcinoma is one of the leading causes of cancer-related death worldwide and Helicobacter pylori infection is the strongest known risk factor for this disease. Although the stomach was once thought to be a sterile environment, it is now known to house many bacterial species leading to a complex interplay between H. pylori and other residents of the gastric microbiota. In addition to the role of H. pylori virulence factors, host genetic polymorphisms, and diet, it is now becoming clear that components of the gastrointestinal microbiota may also influence H. pylori-induced pathogenesis. In this chapter, we discuss emerging data regarding the gastric microbiota in humans and animal models and alterations that occur to the composition of the gastric microbiota in the presence of H. pylori infection that may augment the risk of developing gastric cancer.

  17. Ghrelin and Helicobacter pylori infection

    Institute of Scientific and Technical Information of China (English)

    Hiroyuki Osawa

    2008-01-01

    Ghrelin is primarily secreted from the stomach and has been implicated in the coordination of eating behavior and weight regulation. Ghrelin also plays an essential role in the mechanism of gastric mucosal defense. Thus, it is important to clarify which diseases primar-ily influence changes in plasma ghrelin concentrations. Helicobacter pylori(H pylori infection is involved in the pathogenesis of gastritis, gastric and duodenal ulcer, gastric carcinoma, and mucosa-associated lym-phoid tissue lymphorna. H pylori eradication is related to body weight change. Compared, H pylori infected and negative subjects with normal body mass index, plasma ghrelin concentration, gastric ghrelin mRNA, and the number of ghrelin producing cells in gastric mucosa are significantly lower in Hpylori injected sub-jects than in H pylori-negative controls. Plasma ghrelin concentration decreases with the progression of gastric atrophy. Impaired gastric ghrelin production in associa-tion with atrophic gastritis induced by Hpylori infection accounts for the decrease in plasma ghrelin concentra-tion. However, the ratio of plasma acylated ghrelin to total ghrelin levels is higher in patients with chronic atrophic gastritis than in healthy subjects. This may re-sult from the compensatory increase in plasma active ghrelin concentration in response to gastric atrophy. After H pylori eradication, gastric preproghrelin mRNA expression is increased nearly 4-fold in most cases. However, changes in plasma ghrelin concentrations be-fore and after H pylori cure are not associated with the gastric ghrelin production. Plasma ghrelin changes are inversely correlated with both body weight change and initial plasma ghrelin levels.

  18. Helicobacter pylori eradication for preventing gastric cancer.

    Science.gov (United States)

    Lu, Bin; Li, Meng

    2014-05-21

    Helicobacter pylori (H. pylori) infection is a major risk factor for gastric cancer (GC) development, which is one of the most challenging malignant diseases worldwide with limited treatments. In the multistep pathogenesis of GC, H. pylori infection slowly induces chronic active gastritis, which progresses through the premalignant stages of atrophic gastritis, intestinal metaplasia, and dysplasia, and then finally to GC. Although eradication of H. pylori is a reasonable approach for the prevention of GC, there have been some contradictory reports, with only some long-term follow-up data showing efficacy of this approach. The inconsistencies are likely due to the insufficient number of participants, relatively short follow-up periods, poor quality of study designs, and the degree and extent of preneoplastic changes at the time of H. pylori eradication. This review analyzes recent high-quality studies to resolve the discrepancies regarding the eradication of H. pylori for GC prevention. The relationship between H. pylori eradication and GC/precancerous lesions/metachronous GC is examined, and the cost-effectiveness of this strategy in the prevention of GC is assessed. Although it is assumed that eradication of H. pylori has the potential to prevent GC, the feasibility and appropriate timing of this strategy for cancer prevention remain to be determined. As a result, additional well-designed trials with longer follow-up periods are needed to clarify this issue.

  19. Molecular mimicry in Helicobacter pylori infections

    Science.gov (United States)

    Chmiela, Magdalena; Gonciarz, Weronika

    2017-01-01

    Gram-negative bacteria Helicobacter pylori (H. pylori) colonize gastric mucosa in humans and increase the risk of serious diseases such as gastric and duodenal ulcers, stomach cancers and mucosa associated lymphoid tissue lymphoma. The role of H. pylori infection in the pathogenesis of several extragastric diseases has been suggested including immune thrombocytopenic purpura, iron deficiency anemia, vitamin D deficiency, cardiovascular diseases, diabetes mellitus and dermatological disorders. Also neurological diseases and even lung cancer have attracted researchers concern. The relation between H. pylori infection and a growth retardation in children has also been suggested. Many mechanisms of molecular mimicry between H. pylori and the host have been proposed as a pathogen strategy to manipulate the immune system of the host in order to remain unrecognized and avoid eradication. A lot of effort has been put into the demonstration of homologous sequences between H. pylori and host compounds. However, knowledge about how often autoantibodies or autoreactive T lymphocytes induced during H. pylori infections cause pathological disorders is insufficient. This review provides data on H. pylori antigenic mimicry and possible deleterious effects due to the induction of immune response to the components common to these bacteria and the host. PMID:28652651

  20. Molecular mimicry in Helicobacter pylori infections.

    Science.gov (United States)

    Chmiela, Magdalena; Gonciarz, Weronika

    2017-06-14

    Gram-negative bacteria Helicobacter pylori (H. pylori) colonize gastric mucosa in humans and increase the risk of serious diseases such as gastric and duodenal ulcers, stomach cancers and mucosa associated lymphoid tissue lymphoma. The role of H. pylori infection in the pathogenesis of several extragastric diseases has been suggested including immune thrombocytopenic purpura, iron deficiency anemia, vitamin D deficiency, cardiovascular diseases, diabetes mellitus and dermatological disorders. Also neurological diseases and even lung cancer have attracted researchers concern. The relation between H. pylori infection and a growth retardation in children has also been suggested. Many mechanisms of molecular mimicry between H. pylori and the host have been proposed as a pathogen strategy to manipulate the immune system of the host in order to remain unrecognized and avoid eradication. A lot of effort has been put into the demonstration of homologous sequences between H. pylori and host compounds. However, knowledge about how often autoantibodies or autoreactive T lymphocytes induced during H. pylori infections cause pathological disorders is insufficient. This review provides data on H. pylori antigenic mimicry and possible deleterious effects due to the induction of immune response to the components common to these bacteria and the host.

  1. Medicinal plant activity on Helicobacter pylori related diseases

    Science.gov (United States)

    Wang, Yuan-Chuen

    2014-01-01

    More than 50% of the world population is infected with Helicobacter pylori (H. pylori). The bacterium highly links to peptic ulcer diseases and duodenal ulcer, which was classified as a group I carcinogen in 1994 by the WHO. The pathogenesis of H. pylori is contributed by its virulence factors including urease, flagella, vacuolating cytotoxin A (VacA), cytotoxin-associated gene antigen (Cag A), and others. Of those virulence factors, VacA and CagA play the key roles. Infection with H. pylori vacA-positive strains can lead to vacuolation and apoptosis, whereas infection with cagA-positive strains might result in severe gastric inflammation and gastric cancer. Numerous medicinal plants have been reported for their anti-H. pylori activity, and the relevant active compounds including polyphenols, flavonoids, quinones, coumarins, terpenoids, and alkaloids have been studied. The anti-H. pylori action mechanisms, including inhibition of enzymatic (urease, DNA gyrase, dihydrofolate reductase, N-acetyltransferase, and myeloperoxidase) and adhesive activities, high redox potential, and hydrophilic/hydrophobic natures of compounds, have also been discussed in detail. H. pylori-induced gastric inflammation may progress to superficial gastritis, atrophic gastritis, and finally gastric cancer. Many natural products have anti-H. pylori-induced inflammation activity and the relevant mechanisms include suppression of nuclear factor-κB and mitogen-activated protein kinase pathway activation and inhibition of oxidative stress. Anti-H. pylori induced gastric inflammatory effects of plant products, including quercetin, apigenin, carotenoids-rich algae, tea product, garlic extract, apple peel polyphenol, and finger-root extract, have been documented. In conclusion, many medicinal plant products possess anti-H. pylori activity as well as an anti-H. pylori-induced gastric inflammatory effect. Those plant products have showed great potential as pharmaceutical candidates for H. pylori

  2. N-acetylcysteine, a novel treatment for Helicobacter pylori infection.

    Science.gov (United States)

    Huynh, Hien Quoc; Couper, Richard T L; Tran, Cuong D; Moore, Lynette; Kelso, Richard; Butler, Ross N

    2004-01-01

    N-Acetylcysteine (NAC), being both a mucolytic agent and a thiol-containing antioxidant, may affect the establishment and maintenance of H. pylori infection within the gastric mucus layer and mucosa. Agar and broth dilution susceptibility tests determined the MIC of H. pylori strain SSI to NAC. H. pylori load in SSI strain-infected C57BL mice was determined as colony forming units per gram of gastric tissue. Gastritis assessment was scored and gastric surface hydrophobicity was determined by contact angle measurement. MICs of NAC were 5 to 10 and 10 to 15 mg/ml using the agar dilution and broth dilution methods, respectively. NAC (120 mg per day for 14 days) reduced the H. pylori load in mice by almost 1 log compared with sham treatment. Pretreatment with NAC (40 mg/day) also significantly reduced the H. pylori load but did not prevent H. pylori colonization. Both H. pylori infection and NAC reduced the surface hydrophobicity of murine gastric mucosa. No significant differences were observed in the gastritis scores of H. felis- or H. pylori-infected mice receiving either NAC or sham treatments. This study demonstrates that NAC inhibits the growth of H. pylori in both agar and broth susceptibility tests and in H. pylori-infected mice. NAC did not alter the severity of H. pylori- or H. felis-induced gastritis.

  3. Helicobacter pylori cag pathogenicity island (cagPAI involved in bacterial internalization and IL-8 induced responses via NOD1- and MyD88-dependent mechanisms in human biliary epithelial cells.

    Directory of Open Access Journals (Sweden)

    Wongwarut Boonyanugomol

    Full Text Available Helicobacter pylori infection has been proposed to be associated with various diseases of the hepatobiliary tract, including cancer of the bile duct epithelial cells (cholangiocarcinoma, CCA. The ability of H. pylori bacteria to cause pathogenic effects in these cells has, however, yet to be investigated. Given that the cag pathogenicity island (cagPAI is required for H. pylori pathogenesis in gastric epithelial cells, we investigated wild-type and cag mutant strains for their ability to adhere, be internalized and induce pro-inflammatory responses in two bile duct epithelial cell lines derived from cases of CCA. The findings from these experiments were compared to results obtained with the well-characterized AGS gastric cancer cell line. We showed that the cagPAI encodes factors involved in H. pylori internalization in CCA cells, but not for adhesion to these cells. Consistent with previous studies in hepatocytes, actin polymerization and α5β1 integrin may be involved in H. pylori internalization in CCA cells. As for AGS cells, we observed significantly reduced levels of NF-κB activation and IL-8 production in CCA cells stimulated with either cagA, cagL or cagPAI bacteria, when compared with wild-type bacteria. Importantly, these IL-8 responses could be inhibited via either pre-treatment of cells with antibodies to α5β1 integrins, or via siRNA-mediated knockdown of the innate immune signaling molecules, nucleotide oligomerization domain 1 (NOD1 and myeloid differentiation response gene 88 (MyD88. Taken together, the data demonstrate that the cagPAI is critical for H. pylori pathogenesis in bile duct cells, thus providing a potential causal link for H. pylori in biliary tract disease.

  4. Helicobacter pylori

    DEFF Research Database (Denmark)

    Leth, Peter Mygind

    1992-01-01

    Helicobacter pylori (HP) are Gram-negative spiral bacteria which occur in the human stomach. The bacteria were cultured in vitro for the first time in 1983. It is suspected that the bacteria may cause chronic gastritis of type B and may also be a contributory cause of chronic ulceration and cancer...... of the stomach. The bacteria are accompanied by characteristic inflammatory changes in the gastric mucosa. The significance for gastritis, chronic ulceration, non-ulcer dyspepsia and carcinoma of the stomach is discussed. HP occurs in a great proportion of the population of the world and the frequency increases...

  5. Helicobacter pylori

    DEFF Research Database (Denmark)

    Leth, Peter Mygind

    1992-01-01

    of the stomach. The bacteria are accompanied by characteristic inflammatory changes in the gastric mucosa. The significance for gastritis, chronic ulceration, non-ulcer dyspepsia and carcinoma of the stomach is discussed. HP occurs in a great proportion of the population of the world and the frequency increases......Helicobacter pylori (HP) are Gram-negative spiral bacteria which occur in the human stomach. The bacteria were cultured in vitro for the first time in 1983. It is suspected that the bacteria may cause chronic gastritis of type B and may also be a contributory cause of chronic ulceration and cancer...

  6. Effect of Helicobacter pylori infection on Bax protein expression in patients with gastric precancerous lesions

    Institute of Scientific and Technical Information of China (English)

    Hai-Feng Liu; Wei-Wen Liu; Guo-An Wang; Xiao-Chun Teng

    2005-01-01

    AIM: To investigate the effect of Helicobacter pylori (H pylori) infection on Bax protein expression, and explore the role of H pylori in gastric carcinogenesis.METHODS: H pylori was assessed by rapid urease test and Warthin-Starry method, and expression of Bax protein was examined immunohistochemically in 72 patients with pre-malignant lesions.RESULTS: Bax protein was differently expressed in intestinal metaplasia and gastric dysplasia, and showed 63.99% positivity. The positivity of Bax protein expression in H pylori-positive gastric precancerous lesions (72.3%) was significantly higher than that in H pylori-negative gastric precancerous lesions (48.0%, χ2 = 4.191, P<0.05).H pylori infection was well correlated with the expression of Bax protein in gastric precancerous lesions (r = 0.978,P<0.01). After eradication of H pylori, the positivity of Bax protein expression significantly decreased in H pylori-positive gastric precancerous lesions (χ2= 5.506,P<0.05). In the persisting H pylori-infected patients,the positivity of Bax protein expression was not changed.CONCLUSION: H pylori infection may be involved in the upregulation of Bax gene, which might be one of the mechanisms of H pylori infection-induced gastric epithelial cell apoptosis. H pylori might act as a tumor promoter in the genesis of gastric carcinoma and eradication of H pylori could inhibit gastric carcinogenesis.

  7. "Targeted disruption of the epithelial-barrier by Helicobacter pylori"

    OpenAIRE

    Wroblewski Lydia E; Peek Richard M

    2011-01-01

    Abstract Helicobacter pylori colonizes the human gastric epithelium and induces chronic gastritis, which can lead to gastric cancer. Through cell-cell contacts the gastric epithelium forms a barrier to protect underlying tissue from pathogenic bacteria; however, H. pylori have evolved numerous strategies to perturb the integrity of the gastric barrier. In this review, we summarize recent research into the mechanisms through which H. pylori disrupts intercellular junctions and disrupts the gas...

  8. "Targeted disruption of the epithelial-barrier by Helicobacter pylori"

    Directory of Open Access Journals (Sweden)

    Wroblewski Lydia E

    2011-11-01

    Full Text Available Abstract Helicobacter pylori colonizes the human gastric epithelium and induces chronic gastritis, which can lead to gastric cancer. Through cell-cell contacts the gastric epithelium forms a barrier to protect underlying tissue from pathogenic bacteria; however, H. pylori have evolved numerous strategies to perturb the integrity of the gastric barrier. In this review, we summarize recent research into the mechanisms through which H. pylori disrupts intercellular junctions and disrupts the gastric epithelial barrier.

  9. H. pylori Infection

    Science.gov (United States)

    ... think you may have a high risk of stomach cancer, talk to your doctor. Together you can decide whether you may benefit from H. pylori screening. References H. pylori and peptic ulcers. National Institute ...

  10. Helicobacter pylori HP(2-20) induces eosinophil activation and accumulation in superficial gastric mucosa and stimulates VEGF-alpha and TGF-beta release by interacting with formyl-peptide receptors.

    Science.gov (United States)

    Prevete, N; Rossi, F W; Rivellese, F; Lamacchia, D; Pelosi, C; Lobasso, A; Necchi, V; Solcia, E; Fiocca, R; Ceppa, P; Staibano, S; Mascolo, M; D'Argenio, G; Romano, M; Ricci, V; Marone, G; De Paulis, A

    2013-01-01

    Eosinophils participate in the immune response against Helicobacter pylori, but little is known about their role in the gastritis associated to the infection. We recently demonstrated that the Hp(2-20) peptide derived from H. pylori accelerates wound healing of gastric mucosa by interacting with N-formyl peptide receptors (FPRs) expressed on gastric epithelial cells. The aim of the present study was to investigate whether eosinophils play a role in the repair of gastric mucosa tissue during H. pylori infection. Immuno-histochemistry and transmission electron microscopy were used to detect eosinophils in gastric mucosal biopsies. Eosinophil re-distribution occurred in the gastric mucosa of H. pylori-infected patients: their density did not change in the deep mucosal layer, whereas it increased in the superficial lamina propria just below the foveolar epithelium; eosinophils entered the epithelium itself as well as the lumen of foveolae located close to the area harboring bacteria, which in turn were also engulfed by eosinophils. The H. pylori-derived peptide Hp(2-20) stimulated eosinophil migration through the engagement of FPR2 and FPR3, and also induced production of VEGF-A and TGF-beta, two key mediators of tissue remodelling. We also demonstrate that Hp(2-20) in vivo induced eosinophil infiltration in rat gastric mucosa after injury brought about by indomethacin. This study suggests that eosinophil infiltrate could modulate the capacity of gastric mucosa to maintain or recover its integrity thereby shedding light on the role of eosinophils in H. pylori infection.

  11. Role of Helicobacter pylori in gastric cancer: Updates

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Helicobacter pylori (H. pylori ) infection is highly prevalentin human, affecting nearly half of the world'spopulation; however, infection remains asymptomaticin majority of population. During its co-existence withhumans, H. pylori has evolved various strategies tomaintain a mild gastritis and limit the immune responseof host. On the other side, presence of H. pylori is alsoassociated with increased risk for the development ofvarious gastric pathologies including gastric cancer (GC).A complex combination of host genetics, environmentalagents, and bacterial virulence factors are consideredto determine the susceptibility as well as the severityof outcome in a subset of individuals. GC is one of themost common cancers and considered as the third mostcommon cause of cancer related death worldwide. Manystudies had proved H. pylori as an important risk factorin the development of non-cardia GC. Although both H.pylori infection and GC are showing decreasing trendsin the developed world, they still remain a major threatto human population in the developing countries. Thecurrent review attempts to highlight recent progress inthe field of research on H. pylori induced GC and aimsto provide brief insight into H. pylori pathogenesis,the role of major virulence factors of H. pylori thatmodulates the host environment and transform thenormal gastric epithelium to neoplastic one. This reviewalso emphasizes on the mechanistic understanding ofhow colonization and various virulence attributes of H.pylori as well as the host innate and adaptive immuneresponses modulate the diverse signaling pathways thatleads to different disease outcomes including GC.

  12. In Helicobacter pylori auto-inducer-2, but not LuxS/MccAB catalysed reverse transsulphuration, regulates motility through modulation of flagellar gene transcription

    Directory of Open Access Journals (Sweden)

    Doherty Neil

    2010-08-01

    Full Text Available Abstract Background LuxS may function as a metabolic enzyme or as the synthase of a quorum sensing signalling molecule, auto-inducer-2 (AI-2; hence, the mechanism underlying phenotypic changes upon luxS inactivation is not always clear. In Helicobacter pylori, we have recently shown that, rather than functioning in recycling methionine as in most bacteria, LuxS (along with newly-characterised MccA and MccB, synthesises cysteine via reverse transsulphuration. In this study, we investigated whether and how LuxS controls motility of H. pylori, specifically if it has its effects via luxS-required cysteine metabolism or via AI-2 synthesis only. Results We report that disruption of luxS renders H. pylori non-motile in soft agar and by microscopy, whereas disruption of mccAHp or mccBHp (other genes in the cysteine provision pathway does not, implying that the lost phenotype is not due to disrupted cysteine provision. The motility defect of the ΔluxSHp mutant was complemented genetically by luxSHp and also by addition of in vitro synthesised AI-2 or 4, 5-dihydroxy-2, 3-pentanedione (DPD, the precursor of AI-2. In contrast, exogenously added cysteine could not restore motility to the ΔluxSHp mutant, confirming that AI-2 synthesis, but not the metabolic effect of LuxS was important. Microscopy showed reduced number and length of flagella in the ΔluxSHp mutant. Immunoblotting identified decreased levels of FlaA and FlgE but not FlaB in the ΔluxSHp mutant, and RT-PCR showed that the expression of flaA, flgE, motA, motB, flhA and fliI but not flaB was reduced. Addition of DPD but not cysteine to the ΔluxSHp mutant restored flagellar gene transcription, and the number and length of flagella. Conclusions Our data show that as well as being a metabolic enzyme, H. pylori LuxS has an alternative role in regulation of motility by modulating flagellar transcripts and flagellar biosynthesis through production of the signalling molecule AI-2.

  13. Helicobacter pylori antigen HP0986 (TieA) interacts with cultured gastric epithelial cells and induces IL8 secretion via NF-κB mediated pathway.

    Science.gov (United States)

    Devi, Savita; Ansari, Suhail A; Vadivelu, Jamuna; Mégraud, Francis; Tenguria, Shivendra; Ahmed, Niyaz

    2014-02-01

    The envisaged roles and partly understood functional properties of Helicobacter pylori protein HP0986 are significant in the context of proinflammatory and or proapoptotic activities, the two important facilitators of pathogen survival and persistence. In addition, sequence analysis of this gene predicts a restriction endonuclease function which remained unknown thus far. To evaluate the role of HP0986 in gastric inflammation, we studied its expression profile using a large number of clinical isolates but a limited number of biopsies and patient sera. Also, we studied antigenic role of HP0986 in altering cytokine responses of human gastric epithelial (AGS) cells including its interaction with and localization within the AGS cells. For in vitro expression study of HP0986, 110 H. pylori clinical isolates were cultured from patients with functional dyspepsia. For expression analysis by qRT PCR of HP0986, 10 gastric biopsy specimens were studied. HP0986 was also used to detect antibodies in patient sera. AGS cells were incubated with recombinant HP0986 to determine cytokine response and NF-κB activation. Transient transfection with HP0986 cloned in pEGFPN1 was used to study its subcellular localization or homing in AGS cells. Out of 110 cultured H. pylori strains, 34 (31%) were positive for HP0986 and this observation was correlated with in vitro expression profiles. HP0986 mRNA was detected in 7 of the 10 biopsy specimens. Further, HP0986 induced IL-8 secretion in gastric epithelial cells in a dose and time-dependent manner via NF-κB pathway. Serum antibodies against HP0986 were positively associated with H. pylori positive patients. Transient transfection of AGS cells revealed both cytoplasmic and nuclear localization of HP0986. HP0986 was moderately prevalent in clinical isolates and its expression profile in cultures and gastric biopsies points to its being naturally expressed. Collective observations including the induction of IL-8 via TNFR1 and NF

  14. Helicobacter Pylori Infections

    Science.gov (United States)

    Helicobacter pylori (H. pylori) is a type of bacteria that causes infection in the stomach. It is found in about two-thirds of ... or stool to see if it contains H. pylori. The best treatment is a combination of antibiotics ...

  15. Helicobacter pylori infection affects mitochondrial function and DNA repair, thus, mediating genetic instability in gastric cells

    DEFF Research Database (Denmark)

    Machado, Ana Manuel Dantas; Madsen, Claus Desler; Bøggild, Cecilie Sisse Line

    2013-01-01

    Helicobacter pylori infection is an important factor for the development of atrophic gastritis and gastric carcinogenesis. However, the mechanisms explaining the effects of H. pylori infection are not fully elucidated. H. pylori infection is known to induce genetic instability in both nuclear...

  16. Helicobacter pylori infection affects mitochondrial function and DNA repair, thus, mediating genetic instability in gastric cells

    DEFF Research Database (Denmark)

    Machado, Ana Manuel Dantas; Madsen, Claus Desler; Bøggild, Cecilie Sisse Line

    2013-01-01

    Helicobacter pylori infection is an important factor for the development of atrophic gastritis and gastric carcinogenesis. However, the mechanisms explaining the effects of H. pylori infection are not fully elucidated. H. pylori infection is known to induce genetic instability in both nuclear and...

  17. Catechins and Sialic Acid Attenuate Helicobacter pylori-Triggered Epithelial Caspase-1 Activity and Eradicate Helicobacter pylori Infection

    Directory of Open Access Journals (Sweden)

    Jyh-Chin Yang

    2013-01-01

    Full Text Available The inflammasome/caspase-1 signaling pathway in immune cells plays a critical role in bacterial pathogenesis; however, the regulation of this pathway in the gastric epithelium during Helicobacter pylori infection is yet to be elucidated. Here, we investigated the effect of catechins (CAs, sialic acid (SA, or combination of CA and SA (CASA on H. pylori-induced caspase-1-mediated epithelial damage, as well as H. pylori colonization in vitro (AGS cells and in vivo (BALB/c mice. Our results indicate that the activity of caspase-1 and the expression of its downstream substrate IL-1β were upregulated in H. pylori-infected AGS cells. In addition, we observed increased oxidative stress, NADPH oxidase gp91phox, CD68, caspase-1/IL-1β, and apoptosis, but decreased autophagy, in the gastric mucosa of H. pylori-infected mice. We have further demonstrated that treatment with CASA led to synergistic anti-H. pylori activity and was more effective than treatment with CA or SA alone. In particular, treatment with CASA for 10 days eradicated H. pylori infection in up to 95% of H. pylori-infected mice. Taken together, we suggest that the pathogenesis of H. pylori involves a gastric epithelial inflammasome/caspase-1 signaling pathway, and our results show that CASA was able to attenuate this pathway and effectively eradicate H. pylori infection.

  18. Autophagy-related genes in Helicobacter pylori infection.

    Science.gov (United States)

    Tanaka, Shingo; Nagashima, Hiroyuki; Uotani, Takahiro; Graham, David Y; Yamaoka, Yoshio

    2017-06-01

    In vitro studies have shown that Helicobacter pylori (H. pylori) infection induces autophagy in gastric epithelial cells. However, prolonged exposure to H. pylori reduces autophagy by preventing maturation of the autolysosome. The alterations of the autophagy-related genes in H. pylori infection are not yet fully understood. We analyzed autophagy-related gene expression in H. pylori-infected gastric mucosa compared with uninfected gastric mucosa obtained from 136 Bhutanese volunteers with mild dyspeptic symptoms. We also studied single nucleotide polymorphisms (SNPs) of autophagy-related gene in 283 Bhutanese participants to identify the influence on susceptibility to H. pylori infection. Microarray analysis of 226 autophagy-related genes showed that 16 genes were upregulated (7%) and nine were downregulated (4%). We used quantitative reverse transcriptase polymerase chain reaction to measure mRNA levels of the downregulated genes (ATG16L1, ATG5, ATG4D, and ATG9A) that were core molecules of autophagy. ATG16L1 and ATG5 mRNA levels in H. pylori-positive specimens (n=86) were significantly less than those in H. pylori-negative specimens (n=50). ATG16L1 mRNA levels were inversely related to H. pylori density. We also compared SNPs of ATG16L1 (rs2241880) among 206 H. pylori-positive and 77 H. pylori-negative subjects. The odds ratio for the presence of H. pylori in the GG genotype was 0.40 (95% CI: 0.18-0.91) relative to the AA/AG genotypes. Autophagy-related gene expression profiling using high-throughput microarray analysis indicated that downregulation of core autophagy machinery genes may depress autophagy functions and possibly provide a better intracellular habit for H. pylori in gastric epithelial cells. © 2017 John Wiley & Sons Ltd.

  19. Influence of efflux pump inhibitors on the multidrug resistance of Helicobacter pylori

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To evaluate the effect of efflux pump inhibitors (EPIs) on multidrug resistance of Helicobacter pylori (H. pylori).METHODS: H. pylori strains were isolated and cultured on Brucella agar plates with 10% sheep's blood. The multidrug resistant (MDR) H. pylori were obtained with the inducer chloramphenicol by repeated doubling of the concentration until no colony was seen, then the susceptibilities of the MDR strains and their parents to 9 antibiotics were assessed with agar dilution tests. The present stud...

  20. Helicobacter pylori infection generates genetic instability in gastric cells

    DEFF Research Database (Denmark)

    Machado, Ana Manuel Dantas; Figueiredo, Céu; Seruca, Raquel

    2010-01-01

    The discovery that Helicobacter pylori is associated with gastric cancer has led to numerous studies that investigate the mechanisms by which H. pylori induces carcinogenesis. Gastric cancer shows genetic instability both in nuclear and mitochondrial DNA, besides impairment of important DNA repair...

  1. Host pathogen interactions in Helicobacter pylori related gastric cancer

    Science.gov (United States)

    Chmiela, Magdalena; Karwowska, Zuzanna; Gonciarz, Weronika; Allushi, Bujana; Stączek, Paweł

    2017-01-01

    Helicobacter pylori (H. pylori), discovered in 1982, is a microaerophilic, spiral-shaped gram-negative bacterium that is able to colonize the human stomach. Nearly half of the world's population is infected by this pathogen. Its ability to induce gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma has been confirmed. The susceptibility of an individual to these clinical outcomes is multifactorial and depends on H. pylori virulence, environmental factors, the genetic susceptibility of the host and the reactivity of the host immune system. Despite the host immune response, H. pylori infection can be difficult to eradicate. H. pylori is categorized as a group I carcinogen since this bacterium is responsible for the highest rate of cancer-related deaths worldwide. Early detection of cancer can be lifesaving. The 5-year survival rate for gastric cancer patients diagnosed in the early stages is nearly 90%. Gastric cancer is asymptomatic in the early stages but always progresses over time and begins to cause symptoms when untreated. In 97% of stomach cancer cases, cancer cells metastasize to other organs. H. pylori infection is responsible for nearly 60% of the intestinal-type gastric cancer cases but also influences the development of diffuse gastric cancer. The host genetic susceptibility depends on polymorphisms of genes involved in H. pylori-related inflammation and the cytokine response of gastric epithelial and immune cells. H. pylori strains differ in their ability to induce a deleterious inflammatory response. H. pylori-driven cytokines accelerate the inflammatory response and promote malignancy. Chronic H. pylori infection induces genetic instability in gastric epithelial cells and affects the DNA damage repair systems. Therefore, H. pylori infection should always be considered a pro-cancerous factor. PMID:28321154

  2. Integrin engagement by the helical RGD motif of the Helicobacter pylori CagL protein is regulated by pH-induced displacement of a neighboring helix.

    Science.gov (United States)

    Bonsor, Daniel A; Pham, Kieu T; Beadenkopf, Robert; Diederichs, Kay; Haas, Rainer; Beckett, Dorothy; Fischer, Wolfgang; Sundberg, Eric J

    2015-05-15

    Arginine-aspartate-glycine (RGD) motifs are recognized by integrins to bridge cells to one another and the extracellular matrix. RGD motifs typically reside in exposed loop conformations. X-ray crystal structures of the Helicobacter pylori protein CagL revealed that RGD motifs can also exist in helical regions of proteins. Interactions between CagL and host gastric epithelial cell via integrins are required for the translocation of the bacterial oncoprotein CagA. Here, we have investigated the molecular basis of the CagL-host cell interactions using structural, biophysical, and functional analyses. We solved an x-ray crystal structure of CagL that revealed conformational changes induced by low pH not present in previous structures. Using analytical ultracentrifugation, we found that pH-induced conformational changes in CagL occur in solution and not just in the crystalline environment. By designing numerous CagL mutants based on all available crystal structures, we probed the functional roles of CagL conformational changes on cell surface integrin engagement. Together, our data indicate that the helical RGD motif in CagL is buried by a neighboring helix at low pH to inhibit CagL binding to integrin, whereas at neutral pH the neighboring helix is displaced to allow integrin access to the CagL RGD motif. This novel molecular mechanism of regulating integrin-RGD motif interactions by changes in the chemical environment provides new insight to H. pylori-mediated oncogenesis.

  3. Helicobacter pylori damages human gallbladder epithelial cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Dong-Feng Chen; Lu Hu; Ping Yi; Wei-Wen Liu; Dian-Chun Fang; Hong Cao

    2008-01-01

    AIM: To study the mechanism by which Helicobacter pylori (Hpy/orO damages human gallbladder epithelial cells (HGBEC).METHODS: H pylori isolated from gallbladder were cultured in a liquid medium. Different concentration supernatants and sonicated extracts of H pylori cells were then added to HGBEC in a primary culture. The morphological changes in HGBEC as well as changes in the levels of alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and glutamyltransferase (GGT)were measured.RESULTS: According to the culture curve of HGBEC,it was convenient to study the changes in HGBEC by adding H pylori sonicated extracts and H pylori culture supernatants. Both H pylori sonicated extracts and H pylori culture supernatants had a significant influence on HGBEC morphology, i.e. HGBEC grew more slowly, their viability decreased and their detachment increased. Furthermore, HGBEC ruptured and died. The levels of ALP (33.84 ± 6.00 vs 27.01± 4.67, P < 0.05), LDH (168.37 ± 20.84 vs 55.51 ±17.17, P < 0.01) and GGT (42.01 ± 6.18 vs 25.34 ±4.33, P < 0.01) significantly increased in the HGBEC culture supernatant in a time- and concentrationdependent. The damage to HGBEC in Hpylori culture liquid was more significant than that in H pylori sonicated extracts.CONCLUSION: H pylori induces no obvious damage to HGBEC.

  4. Prevention of Gastric Cancer: Eradication of Helicobacter Pylori and Beyond

    Directory of Open Access Journals (Sweden)

    Tetsuya Tsukamoto

    2017-08-01

    Full Text Available Although its prevalence is declining, gastric cancer remains a significant public health issue. The bacterium Helicobacter pylori is known to colonize the human stomach and induce chronic atrophic gastritis, intestinal metaplasia, and gastric cancer. Results using a Mongolian gerbil model revealed that H. pylori infection increased the incidence of carcinogen-induced adenocarcinoma, whereas curative treatment of H. pylori significantly lowered cancer incidence. Furthermore, some epidemiological studies have shown that eradication of H. pylori reduces the development of metachronous cancer in humans. However, other reports have warned that human cases of atrophic metaplastic gastritis are already at risk for gastric cancer development, even after eradication of these bacteria. In this article, we discuss the effectiveness of H. pylori eradication and the morphological changes that occur in gastric dysplasia/cancer lesions. We further assess the control of gastric cancer using various chemopreventive agents.

  5. Crystal structure of TNF-α-inducing protein from Helicobacter pylori in active form reveals the intrinsic molecular flexibility for unique DNA-binding.

    Directory of Open Access Journals (Sweden)

    Mingming Gao

    Full Text Available Tipα (TNF-α-inducing protein from Helicobacter pylori is a carcinogenic effector. Studies on this protein revealed that a homodimer linked by a pair of intermolecular disulfide bridges (Cys25-Cys25 and Cys27-Cys27 was absolutely necessary for its biological functions. The activities of Tipα would be abolished when both disulfide bridges were disrupted. The crystal structures of Tipα reported to date, however, were based on inactive, monomeric mutants with their N-terminal, including residues Cys25 and Cys27, truncated. Here we report the crystal structure of H. pylori Tipα protein, TipαN(25, at 2.2Å resolution, in which Cys25 and Cys27 form a pair of inter-chain disulfide bridges linking an active dimer. The disulfide bridges exhibit structural flexibility in the present structure. A series of structure-based mutagenesis, biochemical assays and molecular dynamic simulations on DNA-Tipα interactions reveal that Tipα utilizes the dimeric interface as the DNA-binding site and that residues His60, Arg77 and Arg81 located at the interface are crucial for DNA binding. Tipα could bind to one ssDNA, two ssDNA or one dsDNA in experiments, respectively, in the native or mutant states. The unique DNA-binding activities of Tipα indicate that the intrinsic flexible nature of disulfide bridges could endow certain elasticity to the Tipα dimer for its unique bioactivities. The results shed light on the possible structural mechanism for the functional performances of Tipα.

  6. Pathogenesis of Helicobacter pylori infection.

    Science.gov (United States)

    Camilo, Vania; Sugiyama, Toshiro; Touati, Eliette

    2017-09-01

    Helicobacter pylori is responsible for the most commonly found infection in the world's population. It is the major risk factor for gastric cancer development. Numerous studies published over the last year provide new insights into the strategies employed by H. pylori to adapt to the extreme acidic conditions of the gastric environment, to establish persistent infection and to deregulate host functions, leading to gastric pathogenesis and cancer. In this review, we report recent data on the mechanisms involved in chemotaxis, on the essential role of nickel in acid resistance and gastric colonization, on the importance of adhesins and Hop proteins and on the role of CagPAI-components and CagA. Among the host functions, a special focus has been made on the escape from immune response, the ability of bacteria to induce genetic instability and modulate telomeres, the mechanism of autophagy and the deregulation of micro RNAs. © 2017 John Wiley & Sons Ltd.

  7. A novel chimeric flagellum fused with the multi-epitope vaccine CTB-UE prevents Helicobacter pylori-induced gastric cancer in a BALB/c mouse model.

    Science.gov (United States)

    Song, Hui; Lv, Xiaobo; Yang, Jue; Liu, Wei; Yang, Huan; Xi, Tao; Xing, Yingying

    2015-11-01

    Helicobacter pylori (H. pylori) infection causes peptic ulcers, gastric adenocarcinoma, and mucosa-associated lymphoid tissue (MALT) lymphoma. The eradication of H. pylori might be an effective means of preventing gastric cancer. A dual-antigen epitope and dual-adjuvant vaccine called CTB-UE-CF (CCF) was constructed by combining a multi-epitope vaccine CTB-UE with a novel chimeric flagellum (CF) to simultaneously activate Toll-like receptor (TLR) 5-agonist activity and preserve the immunogenicity of H. pylori flagellum FlaA. The evaluation of efficacy to reduce H. pylori colonization was performed using BALB/c mice by oral immunization with a triple dose of this vaccine strain. Two weeks after the last immunization, mice were sacrificed to determine specific antibody levels and proinflammatory cytokine production. To determine the presence of H. pylori, we detected the number of H. pylori by real-time quantitative PCR (qPCR) and measured the urease activity in the gastric tissue. The results showed that the immunogenicity and mucosal immune responses of CCF performed significantly better than those of CTB-UE. This dual-antigen epitope and dual-adjuvant system might greatly contribute to the development of a safe and efficient therapeutic vaccine for humans against H. pylori infection.

  8. [Jianpi jiedu recipe inhibited Helicobacter pylori-induced the expression of cyclooxygenase-2 via p38MAPK/ATF-2 signal transduction pathway in human gastric cancer cells].

    Science.gov (United States)

    Liu, Ning-ning; Wang, Yan; Wu, Qiong

    2011-07-01

    To study the effect of Jianpi Jiedu Recipe (JJR) on the expression of cyclooxygenase (COX-2) in Helicobacter pylori (Hp) infected gastric cancer cell line MKN 45, and its regulatory mechanism of p38MAPK signal transduction. The expressions of COX-2 mRNA and protein in human gastric cancer cell line MKN 45 infected by Hp type strain NCTC 11637 and the regulatory effect of JJR containing serum were detected using Real-time fluorescent quantitative polymerase chain reaction (RFQ-PCR) and Western blot. The effects of Hp on COX-2 mRNA and protein expressions in human gastric cancer cell line MKN 45 were observed using blocking p38MAPK signal transduction pathway by p38MAPK specific inhibitor SB203580. The effects of JJR on Hp-infection activated p38MAPK signal transduction pathway and its downstream activating transcription factor 2 (ATF-2) were observed. COX-2 mRNA and protein expressions were obviously higher after human gastric cancer cell line MKN 45 were infected by Hp (PATF-2. Hp infection induced COX-2 expressions of gastric cancer cells via p38MAPK signal transduction pathway. JJR inhibited Hp-induced the expression of COX-2 through regulating p38MAPK/ATF-2 signal transduction pathway, which may be one of its mechanisms in prevention and treatment of Hp-induced gastric cancer.

  9. Effects of sinomenine on the expression of microRNA-155 in 2,4,6-trinitrobenzenesulfonic acid-induced colitis in mice.

    Directory of Open Access Journals (Sweden)

    Qiao Yu

    Full Text Available BACKGROUND: Sinomenine, a pure alkaloid isolated in Chinese medicine from the root of Sinomenium acutum, has been demonstrated to have anti-inflammatory and immunosuppressive effects. MicroRNAs (miRNAs are gradually being recognized as critical mediators of disease pathogenesis via coordinated regulation of molecular effector pathways. METHODOLOGY/FINDINGS: After colitis was induced in mice by instillation of 5% (w/v 2,4,6-trinitrobenzenesulfonic acid (TNBS, sinomenine at a dose of 100 or 200 mg/kg was orally administered once daily for 7 days. We evaluated body weight, survival rate, diarrhea score, histological score and myeloperoxidase (MPO activity. The mRNA and protein expression levels of miR-155, c-Maf, TNF-α and IFN-γ were determined by quantitative RT-PCR and immunohistochemistry, respectively. Sinomenine (100 or 200 mg/kg-treated mice with TNBS-induced colitis were significantly improved in terms of body weight, survival rate, diarrhea score, histological score and MPO activity compared with untreated mice. Both dosages of sinomenine significantly decreased the mRNA and protein expression levels of c-Maf, TNF-α and IFN-γ, which elevated in TNBS-induced colitis. Furthermore, sinomenine at a dose of 200 mg/kg significantly decreased the level of miR-155 expression by 71% (p = 0.025 compared with untreated TNBS-induced colitis in mice. CONCLUSIONS/SIGNIFICANCE: Our study evaluated the effects and potential mechanisms of sinomenine in the anti-inflammatory response via miRNA-155 in mice with TNBS-induced colitis. Our findings suggest that sinomenine has anti-inflammatory effects on TNBS-induced colitis by down-regulating the levels of miR-155 and several related inflammatory cytokines.

  10. NOD1-Mediated Mucosal Host Defense against Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Tomohiro Watanabe

    2010-01-01

    Full Text Available Infection of the stomach with Helicobacter pylori is an important risk factor for gastritis, peptic ulcer, and gastric carcinoma. Although it has been well established that persistent colonization by H. pylori is associated with adaptive Th1 responses, the innate immune responses leading to these Th1 responses are poorly defined. Recent studies have shown that the activation of nucleotide-binding oligomerization domain 1 (NOD1 in gastric epithelial cells plays an important role in innate immune responses against H. pylori. The detection of H. pylori-derived ligands by cytosolic NOD1 induces several host defense factors, including antimicrobial peptides, cytokines, and chemokines. In this paper, we review the molecular mechanisms by which NOD1 contributes to mucosal host defense against H. pylori infection of the stomach.

  11. Treatment of Helicobacter pylori

    Institute of Scientific and Technical Information of China (English)

    Adam Harris

    2001-01-01

    @@ INTRODUCTION Using an evidence-based approach this review discusses the current treatment of Helicobacter pylori infection in patients with peptic ulcer disease, functional (non-ulcer)dyspepsia or gastro-oesophageal reflux disease (GORD).It also briefly addresses the potential role of eradication of H . pylori in preventing gastric cancer .

  12. Activation of IκB Kinase β and NF-κB Is Essential for Helicobacter pylori-Induced Chronic Gastritis in Mongolian Gerbils▿

    Science.gov (United States)

    Yanai, Ayako; Maeda, Shin; Shibata, Wataru; Hikiba, Yohko; Sakamoto, Kei; Nakagawa, Hayato; Ohmae, Tomoya; Hirata, Yoshihiro; Ogura, Keiji; Muto, Susumu; Itai, Akiko; Omata, Masao

    2008-01-01

    The Mongolian gerbil model of Helicobacter pylori infection resembles human gastritis. In this study, we investigated the role of NF-κB activation in H. pylori-infected gerbils. Activated macrophages were significantly increased in H. pylori-infected gastric mucosa and were identified as being important cells with potent activation of NF-κB, which plays an important part in producing proinflammatory cytokines. Macrophage depletion by the administration of clodronate resulted in milder inflammation in gerbils infected with H. pylori. In macrophages, the inhibition of IκB kinase β (IKKβ), which is a critical kinase for NF-κB activation, resulted in lower proinflammatory cytokine expression caused by heat-killed H. pylori cells. Furthermore, treatment with IKKβ inhibitor resulted in milder inflammation in gerbils with H. pylori gastritis. Collectively, our data suggest that H. pylori-mediated gastric inflammation critically depends on the efficient recruitment and activation of macrophages, with sufficient NF-κB activation. PMID:18070894

  13. Helicobacter pylori Infection Induces Anemia, Depletes Serum Iron Storage, and Alters Local Iron-Related and Adult Brain Gene Expression in Male INS-GAS Mice

    OpenAIRE

    2015-01-01

    Iron deficiency anemia (IDA) affects > 500 million people worldwide, and is linked to impaired cognitive development and function in children. Helicobacter pylori, a class 1 carcinogen, infects about half of the world's population, thus creating a high likelihood of overlapping risk. This study determined the effect of H. pylori infection on iron homeostasis in INS-GAS mice. Two replicates of INS-GAS/FVB male mice (n = 9-12/group) were dosed with H. pylori (Hp) strain SS1 or sham dosed at 6-9...

  14. Treatment of Helicobacter Pylori in Children

    Directory of Open Access Journals (Sweden)

    F Famouri

    2014-04-01

    Full Text Available Childrenwith Helicobacter infection need treatment. The aim of treatment is elimination of H.Pylori. Most patients with this infection are asymptomatic and without peptic disease. Treatment and management of these patients are controversy. Conventional Treatment: The best treatment for H. pylori eradication regimens should have cure rates of at least 80%, be without major side effects, and induce minimal bacterial resistance. Antibiotics alone have not achieved this. Luminal acidity influences both the effectiveness of some antimicrobial agents and the survival of the bacteri; thus antibiotics have been combined with acid suppression such as proton pump inhibitors (PPIs, bismuth, or H2 antagonists. The “classic” regimen is treatment twice daily for 7 days with a PPI and clarithromycin plus either amoxicillin or metronidazole Bismuth has been used in the treatment of peptic ulcer disease and 1 part o quadruple therapy for H.Pylori but compliance of children for it is low.   Sequential Therapy  Sequential therapyinvolves dual therapy with a PPI and amoxicillin for 5 days followed sequentially by clarithromycin, Tinidazole and omeperazole for 5 days or other triple therapy for 7 days. This treatment has had 97% efficacy.   Adjunctive Therapies A number of studies have showed the potential benefits of probiotic therapy in H. pylori treatment regimens.Consumption of these drugs accompanied with other medications increase H.Pylori eradication.    

  15. Helicobacter pylori: prospettive per un vaccino

    Directory of Open Access Journals (Sweden)

    Giuseppe Del Giudice

    2003-09-01

    Full Text Available Helicobacter pylori causes one of the most widespread infections worldwide: it affects more than 50% of the human population, and is responsible for serious gastric pathologies such as chronic gastritis, peptic ulcer, atrophic gastritis and, in some individuals, gastric cancer. Current treatments with antibiotics are efficacious, but encounters several drawbacks at the level of compliance, side effects, antibiotic resistance, etc.The availability of vaccines could contribute in reducing the burden of H. pylori associated diseases. Several bacterial antigens have been identified as virulence factors and proposed as potential vaccine candidates. Some of these antigens have been tested in experimental animal models of challenge with H. pylori. The experiments in animals have shown that prophylactic and therapeutic vaccination against H. pylori is indeed feasible. Several open questions still remain concerning the understanding of the host-microbe relationship and the quality of the immune response which should be induced in order to confer protective immunity in man.The answers to these questions will be crucial in helping the preparation of appropriate vaccine formulations able to efficaciously protect humans both prophylactically and therapeutically. A few clinical trials have been carried out so far with still limited results. Other trials in humans are in progress and are planned for the next few years.The final hope is that these new vaccines will show the expected efficacy against H. pylori and will permit the elimination of this pathogen which has cohabited with humans for more than 100,000 years.

  16. Establishment of helicobacter pylori infection cell model and identification of infection-associated microRNAs%幽门螺杆菌感染细胞模型的建立及感染相关microRNAs的筛选鉴定

    Institute of Scientific and Technical Information of China (English)

    刘真; 贾赤宇; 肖斌; 唐彬; 黎伯胜; 毛旭虎; 邹全明

    2011-01-01

    目的:建立稳定的幽门螺杆菌(H.pylori)感染人胃上皮细胞模型;筛选并鉴定H.pylori感染相关microRNAs(miRNAs)的表达,为深入研究感染相关miRNAs的调控作用机制奠定基础.方法:将H.pylori标准株按MOI=100∶1感染人胃上皮细胞,通过检测炎性细胞因子及炎症反应关键酶的表达综合评价感染模型;采用博奥公司miRNAs V3.0芯片分析细胞感染前后miRNAs表达谱变化,运用实时定量PCR技术和Northem杂交对表达显著差异的miRNAs进行分析鉴定.结果:H.pylori感染细胞24 h后,细胞分泌促炎细胞因子IL-8显著升高(P<0.01);启动炎症反应的关键酶COX-2的表达明显增加.芯片数据显示:H.pylori感染引起超过2倍显著差异表达的miRNAs包括:表达上调的PREDICTED-MIR191、mir-155、miR-92b、miR-30b、miR-146a、miR-16等,和表达降低的miR-181b、miR-324.实时定量PCR和Northem杂交结果显示感染相关miR-155和miR-146a在H.pylori感染细胞模型中表达均显著增加(P<0.01).结论:miR-155和miR-146a在感染细胞模型中的表达增加提示二者可能参与H.pylori感染的免疫调控过程.%Objective: To establish stable gastric epithelium cells model infected by Helicobacter pylori (H.pylori), and to screen and identify H.pylori infection- related microRNAs (miRNAs) so as to investigate the regulatory mechanism of miRNAs.Methods: H.pylori were added to cells at a multiplicity of infection of 100∶1.The infection model was monitored by the release of interleukin-8(IL-8) and the expression of COX-2.The expression profile of cellular miRNAs during H.pylori infection were analyzed by microarray (CapitalBio,Beijing).The significantly altered miRNAs were identified by the quantitative RT-PCR and Northern blot assays.Results: After the incubation of H.pylori with the gastric epithelium cells for 24h, IL-8 release and COX-2 protein expression in cells were detected.The expression of miRNAs could be significantly altered during H.pylori

  17. Potential implications of Helicobacter pylori-related neutrophil-activating protein

    Institute of Scientific and Technical Information of China (English)

    Jannis Kountouras; Ioannis Venizelos; Christos Zavos; Georgia Deretzi; Emmanuel Gavalas; Dimitrios Chatzopoulos; Panagiotis Katsinelos; Elena Tsiaousi; Stergios Gagalis; Stergios A Polyzos

    2012-01-01

    Helicobacter pylori (H. pylori) virulence factors promote the release of various chemoattractants/inflammatory mediators, including mainly the neutrophilattractant chemokine interleukin-8 and neutrophilactivating protein (NAP), involved in H. pylori-induced gastric pathologies. Co-administration of Chios mastic gum (CMG), which inhibits H. pylori NAP, with an H. pylori eradication regimen might add clinical benefits against H. pylori-related gastric pathologies, but possibly not CMG as main therapy. Although H. pylori NAP and other H. pylori-related cytotoxins [i.e., vaculating cytotoxin (VacA)] appear to play a major role in generating and maintaining the H. pylori-associated gastric inflammatory response and H. pylori NAP is a promising vaccine candidate against H. pylori infection (H. pylori-I), concerns regarding its potential drawbacks, particularly neurogenic ones, due to possible crossmimicry, should be considered. Possible cross-mimicry between H. pylori NAP and/or bacterial aquaporin (AQP) and neural tissues may be associated with the anti-AQP-4 antibody-related neural damage in multiple sclerosis (MS)/neuromyelitis optica patients. Moreover, the sequence homology found between H. pylori VacA and human Na+/K+-ATPase A subunit suggests that antibodies to VacA involve ion channels in abaxonal Schwann cell plasmalemma resulting in demyelination in some patients. A series of factors have been implicated in inducing blood-brain barrier (BBB) disruption, including inflammatory mediators (e.g., cytokines and chemokines induced by H. pylori-I) and oxidative stress. BBB disruption permits access of AQP4-specific antibodies and T lymphocytes to the central nervous system, thereby playing a major role in multiple sclerosis pathogenesis. Relative studies show a strong association between H. pylori-I and MS. H. pylori-I induces humoral and cellular immune responses that, owing to the sharing of homologous epitopes (molecular mimicry), cross-react with components of

  18. Helicobacter pylori impairs murine dendritic cell responses to infection.

    Directory of Open Access Journals (Sweden)

    Ya-Hui Wang

    Full Text Available BACKGROUND: Helicobacter pylori, a human pathogen associated with chronic gastritis, peptic ulcer and gastric malignancies, is generally viewed as an extracellular microorganism. Here, we show that H. pylori replicates in murine bone marrow derived-dendritic cells (BMDCs within autophagosomes. METHODOLOGY/PRINCIPAL FINDINGS: A 10-fold increase of CFU is found between 2 h and 6 h p.i. in H. pylori-infected BMDCs. Autophagy is induced around the bacterium and participates at late time points of infection for the clearance of intracellular H. pylori. As a consequence of infection, LC3, LAMP1 and MHC class II molecules are retained within the H. pylori-containing vacuoles and export of MHC class II molecules to cell surface is blocked. However, formalin-fixed H. pylori still maintain this inhibitory activity in BMDC derived from wild type mice, but not in from either TLR4 or TLR2-deficient mice, suggesting the involvement of H. pylori-LPS in this process. TNF-alpha, IL-6 and IL-10 expression was also modulated upon infection showing a TLR2-specific dependent IL-10 secretion. No IL-12 was detected favoring the hypothesis of a down modulation of DC functions during H. pylori infection. Furthermore, antigen-specific T cells proliferation was also impaired upon infection. CONCLUSIONS/SIGNIFICANCE: H. pylori can infect and replicate in BMDCs and thereby affects DC-mediated immune responses. The implication of this new finding is discussed for the biological life cycle of H. pylori in the host.

  19. Helicobacter pylori arginase mutant colonizes arginase Ⅱ knockout mice

    Institute of Scientific and Technical Information of China (English)

    Songhee H Kim; Melanie L Langford; Jean-Luc Boucher; Traci L Testerman; David J McGee

    2011-01-01

    AIM: To investigate the role of host and bacterial argi-nases in the colonization of mice by Helicobacter pylori (H. Pylori).METHODS: H. Pylori produces a very powerful urease that hydrolyzes urea to carbon dioxide and ammonium, which neutralizes acid. Urease is absolutely essential to H. Pylori pathogenesis; therefore, the urea substrate must be in ample supply for urease to work efficiently. The urea substrate is most likely provided by arginase activity, which hydrolyzes L-arginine to L-ornithine and urea. Previous work has demonstrated that H. Pylori arginase is surprisingly not required for colonization of wild-type mice. Hence, another in vivo source of the critical urea substrate must exist. We hypothesized that the urea source was provided by host arginase Ⅱ, since this enzyme is expressed in the stomach, and H. Pylori has previously been shown to induce the expres-sion of murine gastric arginase Ⅱ. To test this hypoth-esis, wild-type and arginase (rocF) mutant H. Pylori strain SS1 were inoculated into arginase Ⅱ knockout mice. RESULTS: Surprisingly, both the wild-type and rocF mutant bacteria still colonized arginase Ⅱ knock-out mice. Moreover, feeding arginase Ⅱ knockout mice the host arginase inhibitor S-(2-boronoethyl)-L-cysteine (BEC), while inhibiting > 50% of the host arginase Ⅰactivity in several tissues, did not block the ability of the rocF mutant H. Pylori to colonize. In con-trast, BEC poorly inhibited H. Pylori arginase activity. CONCLUSION: The in vivo source for the essential urea utilized by H. Pylori urease is neither bacterial arginase nor host arginase Ⅱ; instead, either residual host arginase Ⅰor agmatinase is probably responsible.

  20. Role of Helicobacter pylori infection on nutrition and metabolism

    Science.gov (United States)

    Franceschi, Francesco; Annalisa, Tortora; Teresa, Di Rienzo; Giovanna, D’Angelo; Ianiro, Gianluca; Franco, Scaldaferri; Viviana, Gerardi; Valentina, Tesori; Riccardo, Lopetuso Loris; Antonio, Gasbarrini

    2014-01-01

    Helicobacter pylori (H. pylori) is a gram-negative pathogen that is widespread all over the world, infecting more than 50% of the world’s population. It is etiologically associated with non-atrophic and atrophic gastritis, peptic ulcer and shows a deep association with primary gastric B-cell lymphoma and gastric adenocarcinoma. Recently, the medical research focused on the modification of the gastric environment induced by H. pylori infection, possibly affecting the absorption of nutrients and drugs as well as the production of hormones strongly implicated in the regulation of appetite and growth. Interestingly, the absorption of iron and vitamin B12 is impaired by H. pylori infection, while infected subjects have lower basal and fasting serum levels of ghrelin and higher concentration of leptin compared to controls. Since leptin is an anorexigenic hormone, and ghrelin stimulates powerfully the release of growth hormone in humans, H. pylori infection may finally induce growth retardation if acquired very early in the childhood and in malnourished children. This review is focused on the nutritional effects of H. pylori infection, such as the reduced bioavailability or the malabsorbption of essential nutrients, and of gastrointestinal hormones, as well as on the relationship between H. pylori and the metabolic syndrome. PMID:25278679

  1. Bactericidal activity of Pistacia lentiscus mastic gum against Helicobacter pylori.

    Science.gov (United States)

    Marone, P; Bono, L; Leone, E; Bona, S; Carretto, E; Perversi, L

    2001-12-01

    In this study we evaluated the antibacterial activity of mastic gum, a resin obtained from the Pistacia lentiscus tree, against clinical isolates of Helicobacter pylori. The minimal bactericidal concentrations (MBCs) were obtained by a microdilution assay. Mastic gum killed 50% of the strains tested at a concentration of 125 microg/ml and 90% at a concentration of 500 microg/ml. The influence of sub-MBCs of mastic gum on the morphologies of H. pylori was evaluated by transmission electron microscopy. The lentiscus resin induced blebbing, morphological abnormalities and cellular fragmentation in H. pylori cells.

  2. Human immune responses to H. pylori HLA Class II epitopes identified by immunoinformatic methods.

    Directory of Open Access Journals (Sweden)

    Songhua Zhang

    Full Text Available H. pylori persists in the human stomach over decades and promotes several adverse clinical sequelae including gastritis, peptic ulcers and gastric cancer that are linked to the induction and subsequent evasion of chronic gastric inflammation. Emerging evidence indicates that H. pylori infection may also protect against asthma and some other immune-mediated conditions through regulatory T cell effects outside the stomach. To characterize the complexity of the CD4+ T cell response generated during H. pylori infection, computational methods were previously used to generate a panel of 90 predicted epitopes conserved among H. pylori genomes that broadly cover HLA Class II diversity for maximum population coverage. Here, these sequences were tested individually for their ability to induce in vitro responses in peripheral blood mononuclear cells by interferon-γ ELISpot assay. The average number of spot-forming cells/million PBMCs was significantly elevated in H. pylori-infected subjects over uninfected persons. Ten of the 90 peptides stimulated IFN-γ secretion in the H. pylori-infected group only, whereas two out of the 90 peptides elicited a detectable IFN-γ response in the H. pylori-uninfected subjects but no response in the H. pylori-infected group. Cytokine ELISA measurements performed using in vitro PBMC culture supernatants demonstrated significantly higher levels of TNF-α, IL-2, IL-4, IL-6, IL-10, and TGF-β1 in the H. pylori-infected subjects, whereas IL-17A expression was not related to the subjects H. pylori-infection status. Our results indicate that the human T cell responses to these 90 peptides are generally increased in actively H. pylori-infected, compared with H. pylori-naïve, subjects. This information will improve understanding of the complex immune response to H. pylori, aiding rational epitope-driven vaccine design as well as helping identify other H. pylori epitopes with potentially immunoregulatory effects.

  3. Helicobacter pylori infection and low dietary iron alter behavior, induce iron deficiency anemia, and modulate hippocampal gene expression in female C57BL/6 mice

    Science.gov (United States)

    Burns, Monika; Amaya, Aldo; Bodi, Caroline; Ge, Zhongming; Bakthavatchalu, Vasudevan; Ennis, Kathleen; Wang, Timothy C.; Georgieff, Michael

    2017-01-01

    Helicobacter pylori (H.pylori), a bacterial pathogen, is a causative agent of gastritis and peptic ulcer disease and is a strong risk factor for development of gastric cancer. Environmental conditions, such as poor dietary iron resulting in iron deficiency anemia (IDA), enhance H.pylori virulence and increases risk for gastric cancer. IDA affects billions of people worldwide, and there is considerable overlap between regions of high IDA and high H.pylori prevalence. The primary aims of our study were to evaluate the effect of H.pylori infection on behavior, iron metabolism, red blood cell indices, and behavioral outcomes following comorbid H. pylori infection and dietary iron deficiency in a mouse model. C57BL/6 female mice (n = 40) were used; half were placed on a moderately iron deficient (ID) diet immediately post-weaning, and the other half were maintained on an iron replete (IR) diet. Half were dosed with H.pylori SS1 at 5 weeks of age, and the remaining mice were sham-dosed. There were 4 study groups: a control group (-Hp, IR diet) as well as 3 experimental groups (-Hp, ID diet; +Hp, IR diet; +Hp,ID diet). All mice were tested in an open field apparatus at 8 weeks postinfection. Independent of dietary iron status, H.pylori -infected mice performed fewer exploratory behaviors in the open field chamber than uninfected mice (p<0.001). Hippocampal gene expression of myelination markers and dopamine receptor 1 was significantly downregulated in mice on an ID diet (both p<0.05), independent of infection status. At 12 months postinfection, hematocrit (Hct) and hemoglobin (Hgb) concentration were significantly lower in +Hp, ID diet mice compared to all other study groups. H.pylori infection caused IDA in mice maintained on a marginal iron diet. The mouse model developed in this study is a useful model to study the neurologic, behavioral, and hematologic impact of the common human co-morbidity of H. pylori infection and IDA. PMID:28355210

  4. Helicobacter pylori genetic diversity and gastro-duodenal diseases in Malaysia.

    Science.gov (United States)

    Gunaletchumy, Selva Perumal; Seevasant, Indran; Tan, Mun Hua; Croft, Laurence J; Mitchell, Hazel M; Goh, Khean Lee; Loke, Mun Fai; Vadivelu, Jamuna

    2014-12-11

    Helicobacter pylori infection results in diverse clinical conditions ranging from chronic gastritis and ulceration to gastric adenocarcinoma. Among the multiethnic population of Malaysia, Indians consistently have a higher H. pylori prevalence as compared with Chinese and Malays. Despite the high prevalence of H. pylori, Indians have a relatively low incidence of peptic ulcer disease and gastric cancer. In contrast, gastric cancer and peptic ulcer disease incidence is high in Chinese. H. pylori strains from Chinese strains predominantly belong to the hspEAsia subpopulation while Indian/Malay strains mainly belong to the hspIndia subpopulation. By comparing the genome of 27 Asian strains from different subpopulations, we identified six genes associated with risk of H. pylori-induced peptic ulcer disease and gastric cancer. This study serves as an important foundation for future studies aiming to understand the role of bacterial factors in H. pylori-induced gastro-duodenal diseases.

  5. Anti-Helicobacter pylori and antiulcerogenic activity of Aframomum pruinosum seeds on indomethacin-induced gastric ulcer in rats.

    Science.gov (United States)

    Kouitcheu Mabeku, Laure Brigitte; Nanfack Nana, Blandine; Eyoum Bille, Bertrand; Tchuenteu Tchuenguem, Roland; Nguepi, Eveline

    2017-12-01

    Peptic ulcer is one of the most common diseases affecting mankind. Although there are many products used for its treatment, most of these products produce severe adverse reactions requiring the search for novel compounds. Some Afromomum species are used traditionally to cure acute gastritis. To evaluate the antiulcer activity of the methanol extract of Aframomum pruinosum Gagnepain (Zingiberaceae) seeds against two major etiologic agents of peptic ulcer disease; Helicobacter pylori and non-steroidal anti-inflammatory drugs. The anti-Helicobacter activity of A. pruinosum was evaluated using the broth microdilution method. After oral administration of indomethacin (5 mg/kg) for 5 consecutive days, gastric ulcerated animals were divided into control group and five other groups: three groups that recieved respectively 125, 250 and 500 mg/kg of plant extract, the fourth group received Maalox (50 mg/kg) and the fifth group, Misoprostol (100 μg/kg), respectively, for 5 days. Ulcer areas, gastric mucus content and nitric oxide gastric levels of animals were assessed 24 h after this treatment. A. pruinosum extract shows a moderate anti-Helicobacter activity with an MIC value of 128 μg/mL. A. pruinosum extract, like Misoprostol and Maalox, markedly reduces the % of ulcerated area from 8.15 ± 0.33 to 1.71 ± 0.44% (500 mg/kg). It also increased significantly mucus and NO gastric production with respective values of 4.44 ± 1.35 and 965.81 ± 106.74 μmol/g (500 mg/kg). These findings suggest that A. pruinosum methanol extract possesses antiulcer properties as ascertained by the comparative decreases in ulcer areas, increase of mucus and NO gastric production.

  6. Helicobacter pylori in pediatrics.

    Science.gov (United States)

    Homan, Matjaž; Hojsak, Iva; Kolaček, Sanja

    2012-09-01

    This review summarizes important pediatric studies published from April 2011 up to March 2012. Proteomics profile of ulcerogenic Helicobacter pylori strains was defined in the most interesting study of the last year. The antigen stool test is becoming the "gold standard" in prevalence studies, and according to the last epidemiologic studies, the prevalence of H. pylori infection in childhood is not decreasing any more in the developed world. The resistance rate of H. pylori strains is high in children. Therefore, among other important issues concerning H. pylori in pediatrics, guidelines published by ESPGHAN and NASPGHAN last year also recommended culture and susceptibility testing before first-line treatment in areas with high or unknown antibiotic resistance rates.

  7. Immunity and Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Paul Harris

    2011-03-01

    Full Text Available The bacteria called Helicobacter pylori arrived to the American continent 12,000 years ago (1, reaching South America roughly 5,400-4,600 years AC according to research by Pelayo Correa, a Colombian pathologist who found Helicobacter in stool next to Chinchorro mummies in the North of Arica close to the Pacific Ocean. In 2005, Barry Marshall was awarded the Nobel Prize for his studies on Helicobacter pylori together with Robin Warren.

  8. Nitric oxide synthetase and Helicobacter pylori in patients undergoing appendicectomy.

    LENUS (Irish Health Repository)

    Kell, M R

    2012-02-03

    BACKGROUND: This study was designed to determine whether Helicobacter pylori forms part of the normal microenvironment of the appendix, whether it plays a role in the pathogenesis of acute appendicitis, and whether it is associated with increased expression of inducible nitric oxide synthetase (iNOS) in appendicular macrophages. METHODS: Serology for H. pylori was performed on 51 consecutive patients undergoing emergency appendicectomy. Appendix samples were tested for urease activity, cultured and stained for H. pylori, graded according to the degree of inflammatory infiltrate, and probed immunohistochemically for iNOS expression. RESULTS: The mean age of the patients was 21 (range 7-51) years. Seventeen patients (33 per cent) were seropositive for H. pylori but no evidence of H. pylori was found in any appendix specimen. However, an enhanced inflammatory cell infiltration was observed in seropositive patients (P < 0.04) and the expression of macrophage iNOS in the mucosa of normal and inflamed appendix specimens was increased (P < 0.01). CONCLUSION: H. pylori does not colonize the appendix and is unlikely to be a pathogenic stimulus for appendicitis. Priming effects on mucosal immunology downstream from the foregut may occur after infection with H. pylori.

  9. Autoantibodies to gastric mucosa in Helicobacter pylori infection.

    Science.gov (United States)

    Negrini, R; Savio, A; Appelmelk, B J

    1997-07-01

    Although Helicobacter pylori is recognized as the main cause of chronic gastritis and its associated diseases, very little is known about the pathogenetic mechanisms leading to intestinal metaplasia and atrophic gastritis. We reviewed the data regarding the possible pathogenetic role played by the anti-H. pylori immune responses in the genesis of atrophic gastritis and intestinal metaplasia. Although only type A (corpus-restricted atrophic gastritis), often associated to pernicious anemia, is considered autoimmune in nature, abundant evidence supports the presence of cellular and humoral autoimmune responses also in patients with H. pylori infection. In a mechanism known as antigenic mimicry, highly conserved immunogenic molecules expressed by infectious pathogens may act as a trigger for the induction of humoral and cellular immune responses that cross-react with host cellular antigens. Numerous studies support the view that H. pylori is very effective in inducing antigenic mimicry, and antibodies against H. pylori have been found to cross-react with both antral mucosal cells (the membrane of the secretory canalicular structures of the parietal cells) and gastrin-producing cells. Such autoantibodies were detected both in human infections and in experimental work in rodents. The detection of antibodies that cross-react with H. pylori and various components of the gastric mucosa provides strong support to the view that immune responses against H. pylori not only participate in the pathogenetic mechanisms leading to atrophy in the progressive atrophic gastritis associated with Helicobacter infection but also in the corpus-restricted autoimmune gastritis.

  10. Eradication of H pylori for the prevention of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Karolin Trautmann; Manfred Stolte; Stephan Miehlke

    2006-01-01

    Tnfection with H pylori is the most important known etiological factor associated with gastric cancer. While colonization of the gastric mucosa with H pylori results in active and chronic gastritis in virtually all individuals infected, the likelihood of developing gastric cancer depends on environmental, bacterial virulence and host specific factors. The majority of all gastric cancer cases are attributable to H pylori infection and therefore theoretically preventable. There is evidence from animal models that eradication of H pylori at an early time point can prevent gastric cancer development. However, randomized clinical trials exploring the prophylactic effect of H pylori eradication on the incidence of gastric cancer in humans remain sparse and have yielded conflicting results. Better markers for the identification of patientsat risk for H pylori induced gastric malignancy are needed to allow the development of a more efficient public eradication strategy. Meanwhile, screening and treatment of H pylori in first-degree relatives of gastric cancer patients as well as certain high-risk populations might be beneficial.

  11. Differences in the Antigens of Helicobacter pylori Strains Influence on the Innate Immune Response in the In Vitro Experiments

    Directory of Open Access Journals (Sweden)

    Miha Skvarc

    2014-01-01

    Full Text Available The immune response to Helicobacter pylori importantly determines the pathogenesis of infection as well as the success of antibiotic eradication of the bacteria. Strains of H. pylori were gathered from 14 patients who failed to eradicate H. pylori infection with antibiotics—therapy resistant strains (TRS—or from patients who were able to eradicate H. pylori infection—therapy susceptible strains (TSS. The THP-1 cells were stimulated with H. pylori antigens. Cathepsin X expression on THP-1 cells and concentration of cytokines in the supernatant of THP-1 cells were measured with a flow cytometer. TSS H. pylori antigens increased the proportion of cathepsin X positive cells compared to TRS H. pylori antigens. TSS H. pylori antigens induced higher secretion of IL-12 and IL-6 compared to TRS H. pylori antigens (P<0.001; 0.02. Polymyxin B, a lipid A inhibitor, lowered the secretion of IL-12 and IL-6 in TRS and TSS. We demonstrated a H. pylori strain-dependent cathepsin X and cytokine expression that can be associated with H. pylori resistance to eradication due to lack of effective immune response. Differences in lipid A of H. pylori might have an influence on the insufficient immune response, especially on phagocytosis.

  12. Helicobacter pylori and nonmalignant diseases.

    LENUS (Irish Health Repository)

    Alakkari, Alaa

    2012-02-01

    Research published over the past year has documented the continued decline of Helicobacter pylori-related peptic ulcer disease and increased recognition of non-H. pylori, non-steroidal anti-inflammatory drugs ulcer disease--idiopathic ulcers. Despite reduced prevalence of uncomplicated PUD, rates of ulcer complications and associated mortality remain stubbornly high. The role of H. pylori in functional dyspepsia is unclear, with some authors considering H. pylori-associated nonulcer dyspepsia a distinct organic entity. There is increasing acceptance of an inverse relationship between H. pylori and gastroesophageal reflux disease (GERD), but little understanding of how GERD might be more common\\/severe in H. pylori-negative subjects. Research has focused on factors such as different H. pylori phenotypes, weight gain after H. pylori eradication, and effects on hormones such as ghrelin that control appetite.

  13. Copper promotes TFF1-mediated Helicobacter pylori colonization.

    Directory of Open Access Journals (Sweden)

    Sandro Montefusco

    Full Text Available The trefoil peptides (TFF1, TFF2 and TFF3 are a family of small highly conserved proteins that play an essential role in epithelial regeneration within the gastrointestinal tract, where they are mainly expressed. TFF1 expression is strongly induced after mucosal injury and it has been proposed that tff1 functions as a gastric tumor suppressor gene. Several studies confirm that tff1 expression is frequently lost in gastric cancer because of deletions, mutations or methylation of the tff1 promoter. Infection by Helicobacter pylori (H. pylori results in chronic gastritis and it can lead to the development of gastric or duodenal ulcers. Moreover, it is known that there is a strong link to the development of gastric cancer. It has been shown that H. pylori interacts with the dimeric form of TFF1 and that the rough form of lipopolysaccharide mediates this interaction. We have previously reported that the carboxy-terminus of TFF1 is able to specifically bind copper ions (Cu and that Cu binding favours the homodimerization of the peptide, thus enhancing its motogenic activity. Here, we report that the Cu-TFF1 cuprocomplex promotes adherence of H. pylori to epithelial cells. Adherence of H. pylori to gastric adenocarcinoma cells, AGS AC1 cells, induced to hyper-express TFF1 was enhanced compared to noninduced cells. Copper further promoted this interaction. A H. pylori mutant unable to bind TFF1 did not show enhanced infection of induced cells. Cu treatment induced a thickening of the mucus layer produced by the colorectal adenocarcinoma mucus secreting, goblet cells, HT29-E12 and promoted H. pylori colonisation. Finally, SPR analysis shows that the C-terminus of TFF1, involved in the binding of copper, is also able to selectively bind H. pylori RF-LPS.

  14. Urease-positive bacteria in the stomach induce a false-positive reaction in a urea breath test for diagnosis of Helicobacter pylori infection.

    Science.gov (United States)

    Osaki, Takako; Mabe, Katsuhiro; Hanawa, Tomoko; Kamiya, Shigeru

    2008-07-01

    This study investigated the influence of urease-positive non-Helicobacter pylori bacteria on the results of a urea breath test (UBT) to evaluate the diagnostic utility of a UBT using film-coated [(13)C]urea tablets. The UBT was performed in 102 patients treated with a proton pump inhibitor and antibiotics for the eradication of H. pylori. Urease-producing bacteria other than H. pylori were isolated and identified from the oral cavity and stomach. In 4/102 patients, the UBT gave false-positive results. These false-positive results were found to be caused by the presence of urease-positive bacteria in the oral cavity and stomach. Five bacterial species with urease activity (Proteus mirabilis, Citrobacter freundii, Klebsiella pneumoniae, Enterobacter cloacae and Staphylococcus aureus) were subsequently isolated from the oral cavity and/or stomach. As there was no correlation between the in vitro urease activity of urease-positive non-H. pylori bacteria and the UBT value, and all of the patients with a false-positive UBT result were suffering from atrophic gastritis, it is possible that the false-positive results in the UBT were a result of colonization of urease-positive bacteria and gastric hypochlorhydric conditions. Thus, for the diagnosis of H. pylori infection using a UBT, the influence of stomach bacteria must be considered when interpreting the results.

  15. Helicobacter pylori activates the TLR2/NLRP3/caspase-1/IL-18 axis to induce regulatory T-cells, establish persistent infection and promote tolerance to allergens.

    Science.gov (United States)

    Koch, Katrin N; Müller, Anne

    2015-01-01

    The Gram-negative bacterium Helicobacter pylori is both a normal constituent of the human gastric microbiota as well as a pathogen tightly associated with severe gastric disorders. The ability of H. pylori to activate the inflammasome and caspase-1 in antigen-presenting and other cells, and the resulting processing and release of caspase-1-dependent cytokines, impacts both the immunomodulatory and pathogenic activities of H. pylori. This article summarizes recent insights by us and others on the bacterial and host prerequisites of inflammasome activation. H. pylori predominantly activates the NLRP3 inflammasome through a process that requires TLR2-dependent licensing. We identified the urease enzyme, a colonization determinant known to be required for acid adaptation, as critically required for activation of the TLR2/NLRP3/caspase-1 axis. The phenotypes of urease mutants, as well as mouse strains defective for TLR2 or NLRP3, are discussed with respect to their ability to support persistent colonization, immune tolerance and immunity to H. pylori.

  16. Halitosis and Helicobacter pylori infection

    NARCIS (Netherlands)

    Tangerman, A.; Winkel, E. G.; de Laat, L.; van Oijen, A. H.; de Boer, W. A.

    2012-01-01

    There is disagreement about a possible relationship between Helicobacter pylori (H. pylori) infection and objective halitosis, as established by volatile sulfur compounds (VSCs) in the breath. Many studies related to H. pylori used self-reported halitosis, a subjective and unreliable method to detec

  17. Halitosis and Helicobacter pylori infection

    NARCIS (Netherlands)

    Tangerman, A.; Winkel, E. G.; de Laat, L.; van Oijen, A. H.; de Boer, W. A.

    There is disagreement about a possible relationship between Helicobacter pylori (H. pylori) infection and objective halitosis, as established by volatile sulfur compounds (VSCs) in the breath. Many studies related to H. pylori used self-reported halitosis, a subjective and unreliable method to

  18. Serum levels of tumor necrosis factor-α, interleukin-6 and interleukin-8 are not increased in dyspeptic patients with Helicobacter pylori-associated gastritis

    Directory of Open Access Journals (Sweden)

    Taner Bayraktaroğlu

    2004-01-01

    Full Text Available Introduction: Helicobacter pylori (H. pylori is a non-invasive microorganism causing intense gastric mucosal inflammatory and immune reaction. H. pylori-induced gastric mucosal cytokine overproduction has been clearly documented previously. The stomach has a large surface area and continuous spill-over of locally produced cytokines into the blood stream is a possibility. There are few and conflicting data on circulatory proinflammatory cytokine levels in patients with H. pylori infection.

  19. Helicobacter pylori HP0231 Influences Bacterial Virulence and Is Essential for Gastric Colonization.

    Directory of Open Access Journals (Sweden)

    Yu Zhong

    Full Text Available The Dsb protein family is responsible for introducing disulfide bonds into nascent proteins in prokaryotes, stabilizing the structure of many proteins. Helicobacter pylori HP0231 is a Dsb-like protein, shown to catalyze disulfide bond formation and to participate in redox homeostasis. Notably, many H. pylori virulence factors are stabilized by the formation of disulfide bonds. By employing H. pylori HP0231 deficient strains we analyzed the effect of lack of this bacterial protein on the functionality of virulence factors containing putative disulfide bonds. The lack of H. pylori HP0231 impaired CagA translocation into gastric epithelial cells and reduced VacA-induced cellular vacuolation. Moreover, H. pylori HP0231 deficient bacteria were not able to colonize the gastric mucosa of mice, probably due to compromised motility. Together, our data demonstrate an essential function for H. pylori HP0231 in gastric colonization and proper function of bacterial virulence factors related to gastric pathology.

  20. EXTRAGASTRIC AND ORODENTAL MANIFESTATIONS IN PEDIATRIC INFECTION WITH HELICOBACTER PYLORI. A REVIEW

    Directory of Open Access Journals (Sweden)

    Smaranda DIACONESCU

    2015-12-01

    Full Text Available Helicobacter pylori is a worlwide spread infection mostly manifested in childhood. Many - both invasive and non-invasive diagnostic tests - are now available,. The colonisation effect of gastric mucosa and its consequences are well known and studied. H. pylori can also induce extra-gastric manifestations, like iron-deficiency anemia. The role of oral cavity colonisation is not clearly defined, several studies stating that the oral cavity represents a reservoir for H. pyloris. The presence of this rod in the dental plaque may lead to periodontitis, dental caries, dental calculus and tooth loos. Dental treatment associated with eradication therapy decreases the prevalence of oral H. pylori and improves the eradication rate of gastric H. pylori. Dental treatment in H. pylori infection management should be taken into consideration, especially in children and teens.

  1. Gastric angiogenesis and Helicobacter pylori infection

    Directory of Open Access Journals (Sweden)

    I. D. Pousa

    Full Text Available The formation of new blood vessels seen in conditions commonly associated with Helicobacter pylori (H. pylori infection, including gastritis, peptic ulcer, and gastric carcinoma, prompts consideration of a potential relationship between mucosal colonization by this organism and the angiogenic process. H. pylori directly or indirectly damages endothelial cells, which induces a number of changes in the microvasculature of the gastric mucosa. In H. pylori-associated conditions, that is, in gastritis, peptic ulcer and gastric carcinoma, there is an increased concentration of angiogenic factors, and subsequently a formation of new blood vessels. However, this early angiogenesis -which is activated to repair the gastric mucosa- is subsequently inhibited in patients with peptic ulcer, and ulcer healing is thus delayed. This may be due to the antiproliferative action of this organism on endothelial cells. While the angiogenic process becomes inhibited in infected patients with peptic ulcer, it remains seemingly active in those with gastritis or gastric cancer. This fact is in support of the notion suggested by various studies that peptic ulcer and gastric cancer are mutually excluding conditions. In the case of gastric cancer, neoangiogenesis would enhance nutrient and oxygen supply to cancer cells, and thus tumor growth and metastatic spread.

  2. Human β-defensin-3 induction in H pylori-infected gastric mucosal tissues

    Institute of Scientific and Technical Information of China (English)

    K Kawauchi; A Yagihashi; N Tsuji; N Uehara; D Furuya; D Kobayashi; N Watanabe

    2006-01-01

    AIM: To examine human β-defensin-3 (hBD-3)expression in inflamed gastric mucosal tissues or MKN45 gastric cancer cells with or without H pylori infection for better understanding the innate immune response to H pylori.METHODS: We used reverse transcription-polymerase chain reactions and immunohistochemistry to examine hBD-3 expression in inflamed gastric mucosal tissues or MKN45 gastric cancer cells with or without H pylori.Effects of hBD-3 against H pylori were also evaluated.RESULTS: The mean mRNA expression of hBD-3 in H pylori-positive specimens was significantly higher than that in H pylori-negative specimens (P = 0.0002,Mann-Whitney). In addition, unlike uninfected samples,8 of 15 (53.33%) infected mucosal samples expressed hBD-3 protein. H pylori dose-dependently induced mRNA expression of hBD-3 in MKN45 cells, an effect inhibited by adding anti-toil-like receptor (TLR)-4 antibody. HBD-3 protein completely inhibited H pylori growth.CONCLUSION: Our results suggest that like hBD-2,hBD-3 may be involved in the pathophysiology of H pylori-induced gastritis.

  3. Statin Decreases Helicobacter pylori Burden in Macrophages by Promoting Autophagy

    Science.gov (United States)

    Liao, Wei-Chih; Huang, Mei-Zi; Wang, Michelle Lily; Lin, Chun-Jung; Lu, Tzu-Li; Lo, Horng-Ren; Pan, Yi-Jiun; Sun, Yu-Chen; Kao, Min-Chuan; Lim, Hui-Jing; Lai, Chih-Ho

    2017-01-01

    Statins, 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors, have been found to provide protective effects against several bacterial infectious diseases. Although the use of statins has been shown to enhance antimicrobial treated Helicobacter pylori eradication and reduce H. pylori-mediated inflammation, the mechanisms underlying these effects remain unclear. In this study, in vitro and ex vivo macrophage models were established to investigate the molecular pathways involved in statin-mediated inhibition of H. pylori-induced inflammation. Our study showed that statin treatment resulted in a dose-dependent decrease in intracellular H. pylori burden in both RAW264.7 macrophage cells and murine peritoneal exudate macrophages (PEMs). Furthermore, statin yielded enhanced early endosome maturation and subsequent activation of the autophagy pathway, which promotes lysosomal fusion resulting in degradation of sequestered bacteria, and in turn attenuates interleukin (IL)-1β production. These results indicate that statin not only reduces cellular cholesterol but also decreases the H. pylori burden in macrophages by promoting autophagy, consequently alleviating H. pylori-induced inflammation. PMID:28144585

  4. Effects of lactose as an inducer on expression of Helicobacter pylori rUreB and rHpaA,and Escherichia colirLTKA63 and rLTB

    Institute of Scientific and Technical Information of China (English)

    Jie Yan; Shou-Feng Zhao; Ya-Fei Mao; Yi-Hui Luo

    2004-01-01

    AIM: To demonstrate the effect of lactose as an inducer on expression of the recombinant proteins encoded by Helicobacter pylori ureB and hpaA, and Escherichia coli LTB and LTKA63 genes and to determine the optimal expression parameters.METHODS: By using SDS-PAGE and BIO-RAD gel image analysis system, the outputs of the target recombinant proteins expressed by pET32a-ureB-E. coliBL21, pET32ahpaA-E. coliBL21, pET32a-L TKA63-E. coliBL21 and pET32aLTB-E.coliBL21 were measured when using lactose as inducer at different dosages, original bacterial concentrations,various inducing temperatures and times. The results of the target protein expression induced by lactose were compared to those by isopropyl-β-D-thiogalactoside (IPTG).The proteins were expressed in E.coli.RESULTS: Lactose showed higher efficiency of inducing the expression of rHpaA, rUreB, rLTB and rLTKA63 than IPTG. The expression outputs of the target recombinant proteins induced at 37 ℃ were remarkably higher than those at 28 ℃. Other optimal expression parameters for the original bacterial concentrations, dosages of lactose and inducing time were 0.8, 50 g/L and 4 h for rHpaA; 0.8, 100 g/L and 4 h for rLTKA63; 1.2, 100 g/Land 5 h for both rUreB and rLTB, respectively.CONCLUSION: Lactose, a sugar with non-toxicity and low cost, is able to induce the recombinant genes to express the target proteins with higher efficiency than IPTG. The results in this study establish a beneficial foundation for industrial production of H pylori genetic engineering vaccine.

  5. Infection with Helicobacter pylori is associated with protection against tuberculosis.

    Directory of Open Access Journals (Sweden)

    Sharon Perry

    Full Text Available BACKGROUND: Helicobacter pylori, a lifelong and typically asymptomatic infection of the stomach, profoundly alters gastric immune responses, and may benefit the host in protection against other pathogens. We explored the hypothesis that H. pylori contributes to the control of infection with Mycobacterium tuberculosis. METHODOLOGY/PRINCIPAL FINDINGS: We first examined M. tuberculosis-specific IFN-gamma and H. pylori antibody responses in 339 healthy Northern Californians undergoing routine tuberculin skin testing. Of 97 subjects (29% meeting criteria for latent tuberculosis (TB infection (LTBI, 45 (46% were H. pylori seropositive. Subjects with LTBI who were H. pylori-seropositive had 1.5-fold higher TB antigen-induced IFN-gamma responses (p = 0.04, ANOVA, and a more Th-1 like cytokine profile in peripheral blood mononuclear cells, compared to those who were H. pylori seronegative. To explore an association between H. pylori infection and clinical outcome of TB exposure, we evaluated H. pylori seroprevalence in baseline samples from two high risk TB case-contact cohorts, and from cynomolgus macaques experimentally challenged with M. tuberculosis. Compared to 513 household contacts who did not progress to active disease during a median 24 months follow-up, 120 prevalent TB cases were significantly less likely to be H. pylori infected (AOR: 0.55, 95% CI 0.0.36-0.83, p = 0.005, though seroprevalence was not significantly different from non-progressors in 37 incident TB cases (AOR: 1.35 [95% CI 0.63-2.9] p = 0.44. Cynomolgus macaques with natural H. pylori infection were significantly less likely to progress to TB 6 to 8 months after M. tuberculosis challenge (RR: 0.31 [95% CI 0.12-0.80], p = 0.04. CONCLUSIONS/SIGNIFICANCE: H. pylori infection may induce bystander effects that modify the risk of active TB in humans and non-human primates. That immunity to TB may be enhanced by exposure to other microbial agents may have important implications for

  6. The effect of different strains of Helicobacter pylori on platelet aggregation

    Directory of Open Access Journals (Sweden)

    Paul A Corcoran

    2007-01-01

    Full Text Available BACKGROUND AND AIMS: Helicobacter pylori is the major causative agent in peptic ulcer disease and is strongly implicated in the development of gastric cancer. It has also been linked, less strongly, to cardiovascular disease. The mechanisms by which certain strains of H pylori induce platelet aggregation through interactions with platelet glycoprotein Ib have been previously described.

  7. NikR mediates nickel-responsive transcriptional induction of urease expression in Helicobacter pylori

    NARCIS (Netherlands)

    A.H.M. van Vliet (Arnoud); S.W. Poppelaars (Sophie); B.J. Davies; J. Stoof (Jeroen); S. Bereswill (Stefan); M. Kist (Manfred); C.W. Penn (Charles); E.J. Kuipers (Ernst); J.G. Kusters (Johannes)

    2002-01-01

    textabstractThe important human pathogen Helicobacter pylori requires the abundant expression and activity of its urease enzyme for colonization of the gastric mucosa. The transcription, expression, and activity of H. pylori urease were previously demonstrated to be induced by nick

  8. Vitamin C supplementation does not protect L-gulono-gamma-lactone oxidase-deficient mice from Helicobacter pylori-induced gastritis and gastric premalignancy

    Science.gov (United States)

    In human studies, low vitamin C intake has been associated with more severe Helicobacter pylori gastritis and a higher incidence of gastric cancer. However, vitamin C supplementation has not been definitively shown to protect against gastric cancer. Using vitamin C-deficient B6.129P2-Gulo tm1Umc/mmc...

  9. [Alzheimer's disease and Helicobacter pylori infection: a possible link?].

    Science.gov (United States)

    Roubaud Baudron, Claire; Varon, Christine; Mégraud, Francis; Salles, Nathalie

    2016-03-01

    Alzheimer's disease (AD) is associated with Aß peptide and Tau protein deposits, but the initial process inducing the disease and ultimately neurodegeneration has not yet been elucidated. An infectious hypothesis is suggested by the alteration of the blood-brain barrier and the activation of neuroinflammation in the brain, which could play a role, especially in the decrease of Aß peptide clearance. Several viral or bacterial agents have been incriminated, including Helicobacter pylori. Infection by H. pylori is acquired during childhood and often lifetime persisting, inducing a chronic gastric inflammation, which remains asymptomatic in approximately 80% of cases. However H. pylori infection can induce systemic inflammation and increase homocysteine levels, contributing to worsen AD lesions. Association between H. pylori and AD is suggested by 1) epidemiologic studies, which show higher AD prevalence and more pronounced cognitive impairment in infected than in non-infected subjects; 2) experimental studies in murine models: a) in a first study we evaluated the impact of H. pylori infection on the brain of non-AD predisposed C57BL/6J mice. After an 18-month infection, H. pylori induced a significant gastric inflammation but no brain Aβ deposit nor increased neuroinflammation was observed in their brain; b) we currently study the impact of Helicobacter species infection on behavior and cerebral lesions of AD transgenic (APPswe/PS1dE9) mice and their wild type littermate. The results of these studies do not allow to conclude a significant association between AD and H. pylory infection but may contribute to a better understanding of the role of brain neuroinflammation in AD.

  10. Consequences of Helicobacter pylori infection in children

    OpenAIRE

    Pacifico, Lucia; Anania, Caterina; Osborn, John F.; Ferraro, Flavia; Chiesa, Claudio

    2010-01-01

    Although evidence is emerging that the prevalence of Helicobacter pylori (H. pylori) is declining in all age groups, the understanding of its disease spectrum continues to evolve. If untreated, H. pylori infection is lifelong. Although H. pylori typically colonizes the human stomach for many decades without adverse consequences, children infected with H. pylori can manifest gastrointestinal diseases. Controversy persists regarding testing (and treating) for H. pylori infection in children wit...

  11. Consequences of Helicobacter pylori infection in children

    Institute of Scientific and Technical Information of China (English)

    Lucia; Pacifico; Caterina; Anania; John; F; Osborn; Flavia; Ferraro; Claudio; Chiesa

    2010-01-01

    Although evidence is emerging that the prevalence of Helicobacter pylori (H. pylori) is declining in all age groups, the understanding of its disease spectrum continues to evolve. If untreated, H. pylori infection is lifelong. Although H. pylori typically colonizes the hu-man stomach for many decades without adverse con-sequences, children infected with H. pylori can manifest gastrointestinal diseases. Controversy persists regarding testing (and treating) for H. pylori infection in children with recurrent a...

  12. 幽门螺杆菌抑制大鼠乙酸胃溃疡愈合的机制%Mechanism of Helicobacter Pylori Inhibiting the Healing of Acetic Acid-Induced Gastric Ulcer in Rats

    Institute of Scientific and Technical Information of China (English)

    李成军; 夏立丁; 金丽; 王国忠

    2009-01-01

    目的 研究幽门螺杆菌抑制大鼠乙酸胃溃疡愈合的机制.方法 用幽门螺杆菌感染Wistar大鼠,4周后复制出乙酸胃溃疡模型,在溃疡模型复制后的3、8、16天测定胃窦部黏膜G细胞、D细胞的数目、胃液量和pH.结果 Hp+乙酸溃疡组G细胞数目、胃液量高于乙酸溃疡组(P<0.01);D细胞的数目和pH低于乙酸溃疡组(P<0.01).结论 幽门螺杆菌通过增加胃酸分泌抑制溃疡愈合.%Objective To study the mechanism of Helicobacter Pylori inhibiting the healing of acetic acid - induced gastric ulcer in rats. Methods Rats were infected with Helicobacter Pylori and the model of acetic acid gastric ulcer was replicated at 4 weeks after in-fection. Amount of G cell and D cell in mucosa of gastric antrum, quantity of gastric juice and pH were measured at the 3rd,Sth, 16th day after the model was replicated. Results When the group of Hp + acetic acid ulcer compared with the group of acetic acid ulcer, the number of G cell, quantity of gastric juice increased (P < 0.01), and the number of D cell and pH decreased (P < 0.01). Conclusion Helicobacter Pylori inhibits ulcer healing through increasing gastric acid secretion.

  13. Human gastric mucins differently regulate Helicobacter pylori proliferation, gene expression and interactions with host cells.

    Directory of Open Access Journals (Sweden)

    Emma C Skoog

    Full Text Available Helicobacter pylori colonizes the mucus niche of the gastric mucosa and is a risk factor for gastritis, ulcers and cancer. The main components of the mucus layer are heavily glycosylated mucins, to which H. pylori can adhere. Mucin glycosylation differs between individuals and changes during disease. Here we have examined the H. pylori response to purified mucins from a range of tumor and normal human gastric tissue samples. Our results demonstrate that mucins from different individuals differ in how they modulate both proliferation and gene expression of H. pylori. The mucin effect on proliferation varied significantly between samples, and ranged from stimulatory to inhibitory, depending on the type of mucins and the ability of the mucins to bind to H. pylori. Tumor-derived mucins and mucins from the surface mucosa had potential to stimulate proliferation, while gland-derived mucins tended to inhibit proliferation and mucins from healthy uninfected individuals showed little effect. Artificial glycoconjugates containing H. pylori ligands also modulated H. pylori proliferation, albeit to a lesser degree than human mucins. Expression of genes important for the pathogenicity of H. pylori (babA, sabA, cagA, flaA and ureA appeared co-regulated in response to mucins. The addition of mucins to co-cultures of H. pylori and gastric epithelial cells protected the viability of the cells and modulated the cytokine production in a manner that differed between individuals, was partially dependent of adhesion of H. pylori to the gastric cells, but also revealed that other mucin factors in addition to adhesion are important for H. pylori-induced host signaling. The combined data reveal host-specific effects on proliferation, gene expression and virulence of H. pylori due to the gastric mucin environment, demonstrating a dynamic interplay between the bacterium and its host.

  14. Helicobacter pylori Infection in Pediatrics.

    Science.gov (United States)

    Roma, Eleftheria; Miele, Erasmo

    2015-09-01

    This review includes the main pediatric studies published from April 2014 to March 2015. The host response of Treg cells with increases in FOXP3 and TGF-β1 combined with a reduction in IFN-γ by Teff cells may contribute to Helicobacter pylori susceptibility in children. Genotypic variability in H. pylori strains influences the clinical manifestation of the infection. Helicobacter pylori infection is associated with variables indicative of a crowded environment and poor living conditions, while breast-feeding has a protective effect. Intrafamilial infection, especially from mother to children and from sibling to sibling, is the dominant transmission route. Studies showed conflicting results regarding the association between H. pylori infection and iron deficiency anemia. One study suggests that H. pylori eradication plays a role in the management of chronic immune thrombocytopenic purpura in H. pylori-infected children and adolescents. The prevalence of H. pylori was higher in chronic urticaria patients than in controls and, following H. pylori eradication, urticarial symptoms disappeared. An inverse relationship between H. pylori infection and allergic disease was reported. Antibiotic resistance and insufficient compliance to treatment limit the efficacy of eradication therapy. Sequential therapy had no advantage over standard triple therapy. In countries where H. pylori infection is prevalent, studies focusing on virulence factors and antibiotic susceptibility may provide anticipation of the prognosis and may be helpful to reduce morbidity and mortality.

  15. Expression of differential nitric oxide synthase isoforms in human gastric mucosa infected with Helicobacter pylori

    Institute of Scientific and Technical Information of China (English)

    屠振兴; 龚燕芳; 丁华; 许国铭; 李兆申; 满晓华

    2003-01-01

    Objective: To study the relationship between nitric oxide synthase (NOS) expression in human gastric mucosa and Helicobacter pylori (H.pylori) infection. Methods: Gastric mucosa samples were obtained from antrum of 33 patients received gastroendoscopy. H.pylori infection was confirmed by Giems staining and bacteria culture under microaerophilic conditions. Expression of iNOS, eNOS and nitrotyrosine were detected by immunohistochemistry. Results: (1) The positive rate of H. pylori infection was 66.7%(22/33). (2) iNOS positive staining in inflammatory cells was detected in 77.3%(17/22) of samples with H.pylori and 27.3%(3/11) without H.pylori infection (P0.05). (5) Moderate and severe infiltrations of inflammatory cells were found in 86.4%(19/22) of gastric biopsies with H. pylori and 9.1%(1/11) of samples without H. pylori infection (P<0.01). Conclusion: H.pylori infection might promote infiltration of mononuclear cells and macrophages in gastric mucosa and induce iNOS expression in these cells. The accumulated nitric oxide in local area may result in gastric mucosa damage.

  16. Role of γ-glutamyltranspeptidase in the pathogenesis of Helicobacter pylori infection.

    Science.gov (United States)

    Rimbara, Emiko; Mori, Shigetarou; Kim, Hyun; Shibayama, Keigo

    2013-10-01

    γ-Glutamyltranspeptidase and asparaginase have been shown to play important roles in Helicobacter pylori colonization and cell death induced by H. pylori infection. In this study, the association of γ-glutamyltranspeptidase and asparaginase was elucidated by comparing activities of both deamidases in H. pylori strains from patients with chronic gastritis, gastric and duodenal ulcers, and gastric cancer. γ-Glutamyltranspeptidase activities in H. pylori strains from patients with gastric cancer were significantly higher than in those from patients with chronic gastritis or gastric ulcers. There was a wide range of asparaginase activities in H. pylori strains from patients with gastric cancer and these were not significantly than those from patients with other diseases. To identify the contributions of γ-glutamyltranspeptidase and asparaginase to gastric cell inflammation, human gastric epithelial cells (AGS line) were infected with H. pylori wild-type and knockout strains and inflammatory responses evaluated by induction of interleukin-8 (IL-8). IL-8 response was significantly decreased by knockout of the γ-glutamyltranspeptidase-encoding gene but not by knockout of the asparaginase-encoding gene. Additionally, IL-8 induction by infection with the H. pylori wild-type strain was significantly decreased by adding glutamine during infection. These findings indicate that IL-8 induction caused by γ-glutamyltranspeptidase activity in H. pylori is mainly attributable to depletion of glutamine. These data suggest that γ-glutamyltranspeptidase plays a significant role in the chronic inflammation caused by H. pylori infection.

  17. Metabolic Interaction of Helicobacter pylori Infection and Gut Microbiota

    Directory of Open Access Journals (Sweden)

    Yao-Jong Yang

    2016-02-01

    Full Text Available As a barrier, gut commensal microbiota can protect against potential pathogenic microbes in the gastrointestinal tract. Crosstalk between gut microbes and immune cells promotes human intestinal homeostasis. Dysbiosis of gut microbiota has been implicated in the development of many human metabolic disorders like obesity, hepatic steatohepatitis, and insulin resistance in type 2 diabetes (T2D. Certain microbes, such as butyrate-producing bacteria, are lower in T2D patients. The transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome, but the exact pathogenesis remains unclear. H. pylori in the human stomach cause chronic gastritis, peptic ulcers, and gastric cancers. H. pylori infection also induces insulin resistance and has been defined as a predisposing factor to T2D development. Gastric and fecal microbiota may have been changed in H. pylori-infected persons and mice to promote gastric inflammation and specific diseases. However, the interaction of H. pylori and gut microbiota in regulating host metabolism also remains unknown. Further studies aim to identify the H. pylori-microbiota-host metabolism axis and to test if H. pylori eradication or modification of gut microbiota can improve the control of human metabolic disorders.

  18. Analysis of the urinary peptidome associated with Helicobacter pylori infection

    Institute of Scientific and Technical Information of China (English)

    Di Xiao; Fan-Liang Meng; Li-Hua He; Yi-Xin Gu; Jian-Zhong Zhang

    2011-01-01

    AIM: To investigate the relationship between urinary peptide changes and Helicobacter pylori (H. pylori ) infection using urinary peptidome profiling.METHODS: The study was performed in volunteers (n= 137) who gave informed consent. Urinary peptides were enriched by magnetic beads based weak cation exchange chromatography and spectrums acquired by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). ClinProTools bioinformatics software was used for statistical analysis and the recognition of peptide patterns. The marker peptides were identified by LTQ Obitrap XL tandem MS.RESULTS: Approximately 50 proteins or peptides which loaded onto the magnetic beads were detected by MALDI-TOF MS. By optimizing the parameters of the model,the Genetic Algorithm model had good recognition capability (97%) and positive predictive value (94%).Based on the model, 2 markers with molecular masses of 6788 and 1912 Da were found that differentiated between H. pylori positive and negative volunteers.The m/z 1912 sequence was parsed as SKQFTSSTSYNRGDSTF.The peptide was identified as isoform 1 of the fibrinogen α chain precursor, whose concentration in urine was markedly higher in H. pylori infected volunteers than in H. pylori non-infected ones.CONCLUSION: The appearance of urinary fibrinogen degradation products is caused by an active H. pylori -induced process.

  19. Cloning and Expression of Helicobacter pylori HpaA Gene

    Directory of Open Access Journals (Sweden)

    Moein Farshchian

    2009-01-01

    Full Text Available Objective: Helicobacter pylori is associated with chronic gastritis, peptic ulcers, gastric adenocarcinomaand gastric mucosa-associated lymphoid tissue (MALT lymphoma. Antibiotictherapies do not protect from potential re-infection and have a risk for development of drugresistance. Therefore, prophylactic vaccine mediated protection against H. pylori is an attractiveclinical interest. H. pylori adhesin A (HpaA is a conserved surface lipoprotein and playsimportant roles in the pathogenesis of infection. In this study the recombinant protein (rHpaAwas over-expressed in E.coli.Materials and Methods: The hpaA gene was amplified by PCR. Prokaryote expression vectorpET28a-hpaA was constructed, and used to transform E.coli BL21DE3. The expressionof recombinant protein induced by IPTG was examined by SDS-PAGE. Western blot wereused to determine immunoreactivity of rHpaA by a rabbit polyclonal antibodies against wholecell of H. pylori.Results: The hpaA gene nucleotide sequence in the recombinant plasmid vector of pET-28-a-hpaA was consistent with that of H.pylori hpaA as published in the GenBank. SDS-PAGEdemonstrated that the constructed prokaryotic expression efficiently produced rHpaA at the1.5 mmol/L of IPTG. HpaA fusion protein was able to react with the rabbit polyclonal antibodyagainst whole cells of H. pylori.Conclusion: A prokaryotic expression system pET-28a-hpaA-BL21 with high efficiency of H.pylori hpaA gene was successfully established and the HpaA fusion protein showed satisfactoryimmunoreactivity. These results indicate that production of a specific recombinant proteinis an alternative and potentially more expeditious strategy for development of H. pylori vaccine.

  20. Emerging Role of Probiotics in the Management of Helicobacter pylori Infection: Histopathologic Perspectives.

    Science.gov (United States)

    Emara, Mohamed H; Elhawari, Soha A; Yousef, Salem; Radwan, Mohamed I; Abdel-Aziz, Hesham R

    2016-02-01

    There is growing evidence from preclinical and clinical studies that emphasizes the efficacy of probiotics in the management of Helicobacter (H) pylori infection; it increased the eradication rate, improved patient clinical manifestations and lowered treatment associated side effects. In this review we documented the potential ability of probiotics to ameliorate H. pylori induced histological features. We searched the available literature for full length articles focusing the role of probiotics on H. pylori induced gastritis from histologic perspectives. Probiotics lowered H. pylori density at the luminal side of epithelium, improved histological inflammatory and activity scores both in the gastric corpus and antrum. This effect persists for long period of time after discontinuation of probiotic supplementation and this is probably through an immune mechanism. The current evidence support the promising role of probiotics in improving H. pylori induced histopathological features both in gastric antrum and corpus and for long periods of time. Because increased density of H. pylori on the gastric mucosa is linked to more severe gastritis and increased incidence of peptic ulcers, we can infer that a reduction of the density might help to decrease the risk of developing pathologies, probably the progression toward atrophic gastritis and gastric adenocarcinoma. These effects together with improving the H. pylori eradication rates and amelioration of treatment related side effects might open the door for probiotics to be added to H. pylori eradication regimens. © 2015 John Wiley & Sons Ltd.

  1. Helicobacter pylori Activates IL-6-STAT3 Signaling in Human Gastric Cancer Cells: Potential Roles for Reactive Oxygen Species.

    Science.gov (United States)

    Piao, Juan-Yu; Lee, Hee Geum; Kim, Su-Jung; Kim, Do-Hee; Han, Hyeong-Jun; Ngo, Hoang-Kieu-Chi; Park, Sin-Aye; Woo, Jeong-Hwa; Lee, Jeong-Sang; Na, Hye-Kyung; Cha, Young-Nam; Surh, Young-Joon

    2016-10-01

    Recent studies have shown that Helicobacter pylori (H. pylori) activates signal transducer and activator of transcription 3 (STAT3) that plays an important role in gastric carcinogenesis. However, the molecular mechanism underlying H. pylori-mediated STAT3 activation is still not fully understood. In this study, we investigated H. pylori-induced activation of STAT3 signaling in AGS human gastric cancer cells and the underlying mechanism. AGS cells were cocultured with H. pylori, and STAT3 activation was assessed by Western blot analysis, electrophoretic mobility shift assay and immunocytochemistry. To demonstrate the involvement of reactive oxygen species (ROS) in H. pylori-activated STAT3 signaling, the antioxidant N-acetylcysteine was utilized. The expression and production of interleukin-6 (IL-6) were measured by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA), respectively. The interaction between IL-6 and IL-6 receptor (IL-6R) was determined by the immunoprecipitation assay. H. pylori activates STAT3 as evidenced by increases in phosphorylation on Tyr(705) , nuclear localization, DNA binding and transcriptional activity of this transcription factor. The nuclear translocation of STAT3 was also observed in H. pylori-inoculated mouse stomach. In the subsequent study, we found that H. pylori-induced STAT3 phosphorylation was dependent on IL-6. Notably, the increased IL-6 expression and the IL-6 and IL-6R binding were mediated by ROS produced as a consequence of H. pylori infection. H. pylori-induced STAT3 activation is mediated, at least in part, through ROS-induced upregulation of IL-6 expression. These findings provide a novel molecular mechanism responsible for H. pylori-induced gastritis and gastric carcinogenesis. © 2016 John Wiley & Sons Ltd.

  2. Helicobacter pylori infection in Japan

    Science.gov (United States)

    Shiota, Seiji; Murakawi, Kazunari; Suzuki, Rumiko; Fujioka, Toshio; Yamaoka, Yoshio

    2013-01-01

    The prevalence of Helicobacter pylori infection is gradually decreasing in Japan. On the main island of Japan, nearly all H. pylori isolates possess cagA and vacA with strong virulence. However, less virulent H. pylori strains are frequently found in Okinawa where cases of gastric cancer are the lowest in Japan. Eradication therapy for peptic ulcer, idiopathic thrombocytopenic purpura, gastric mucosa-associated lymphoid tissue lymphoma and early gastric cancer after endoscopic resection has been approved by the Japanese national health insurance system. However, the Japanese Society for Helicobacter Research recently stated that all ‘H. pylori infection’ was considered as the indication for eradication irrespective of the background diseases. To eliminate H. pylori in Japan, the Japanese health insurance system should approve the eradication of all H. pylori infections. PMID:23265147

  3. Apoptosis, proliferation and p53 gene expression of H. pylori associated gastric epithelial lesions

    Institute of Scientific and Technical Information of China (English)

    Zhong Zhang1; Yuan Yuan; Hua Gao; Ming Dong; Lan Wang; Yue-Hua Gong

    2001-01-01

    AIM: To study the relationship between Helicobacter pylori (H. Pylori) and gastric carcinoma and its possible pathogenesis by H. Pylori. METHODS: DNEL technique and immunohistochemical technique were used to study the state of apoptosis,proliferation and p53 gene expression. A total of 100 gastric mucosal biopsy specimens, including 20 normal mucosa, 30H. Pylori-negative and 30 H. Pylorf-positive gastric precancerous lesions along with 20 gastric carcinomas were studied. RESULTS: There were several apoptotic cells in the superficial epithelium and a few proliferative cells within the neck of gastric glands, and no p53 protein expression in normal mucosa. In gastric carcinoma, there were few apoptotic cells, while there were a large number of proliferative cells, and expression of p53 protein significantly was increased. In the phase of metaplasia, the apoptotic index (Al, 4.36% ± 1.95%), proliferative index (PI, 19.11% ± 6.79%) and positivity of p53 expression (46.7%) in H. Pylori-positive group were higher than those in normal mucosa (P< 0.01). Al in H. Pylori-positive group was higher than that in H. Pylori-negative group (3.81% ±1.76%), PI in H. Pylori-positive group was higher than that in H. Pylori-negative group (12.25% ±5.63%, P<0.01 ). In the phase of dysplasia, Al (2.31% ± 1.10%) in H. Pylori-positive group was lower (3.05% ± 1.29%) than that in H. Pylori-negative group, but PI (33.89% ± 11.65%)wassignificantly higher(22.09± 8018%, P< 0.01). In phases of metaplasia, dysplasia and gastric cancer in the H. Pylori-positive group, Als had an evidently graduall decreasing trend (P < 0.01 ), while Pis had an evidently gradual increasing trend (P< 0.05 or P< 0.01), and there was also a trend of gradual increase in the expression of p53 gene. CONCLUSION: In the course of the formation of gastric carcinoma, proliferation of gastric mucosa can be greatly increased by H. Pylori, and H. Pylori can induce apoptosis in the phase of metaplasia but in the phase of

  4. Biopatologia do Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Ladeira Marcelo Sady Plácido

    2003-01-01

    Full Text Available A infecção pelo Helicobacter pylori (H. pylori induz inflamação persistente na mucosa gástrica com diferentes lesões orgânicas em humanos, tais como gastrite crônica, úlcera péptica e câncer gástrico. Os fatores determinantes desses diferentes resultados incluem a intensidade e a distribuição da inflamação induzida pelo H. pylori na mucosa gástrica. Evidências recentes demonstram que cepas do H. pylori apresentam diversidade genotípica, cujos produtos acionam o processo inflamatório por meio de mediadores e citocinas, que podem levar a diferentes graus de resposta inflamatória do hospedeiro, resultando em diferentes destinos patológicos. Cepas H. pylori com a ilha de patogenicidade cag induzem resposta inflamatória mais grave, através da ativação da transcrição de genes, aumentando o risco para desenvolvimento de úlcera péptica e câncer gástrico. O estresse oxidativo e nitrosativo induzido pela inflamação desempenha importante papel na carcinogênese gástrica como mediador da formação ou ativação de cancerígenos, danos no DNA, bem como de alterações da proliferação celular e da apoptose.

  5. Pathogenic diversity of Helicobacter pylori.

    Science.gov (United States)

    Mégraud, F

    1997-04-01

    Helicobacter pylori has been shown to possess a very heterogeneous genoma despite its common phenotypic properties. Some characteristics relevant to pathogenesis have also been found to be heterogeneous. This is the case for adherence properties and the amount of urease produced, but it was not possible to relate these properties to disease entities. A vacuolating cytotoxin which alters epithelial cells has been found in about 60% of strains isolated from patients with ulcers versus 30% from those with gastritis only. The cagA gene can be used as a marker to detect the cag pathogenicity island. This DNA fragment seems to induce an increased inflammation in the gastric tissue via release of interleukin 8 by the epithelial cells. The association of this marker is strongly linked with ulcers compared with gastritis only (80% vs 55%, respectively). A number of other properties may be heterogeneous, but the low number of strains studied does not allow conclusions to be drawn.

  6. Use of PCR and culture to detect Helicobacter pylori in naturally infected cats following triple antimicrobial therapy.

    Science.gov (United States)

    Perkins, S E; Yan, L L; Shen, Z; Hayward, A; Murphy, J C; Fox, J G

    1996-06-01

    Helicobacter pylori causes gastritis and peptic ulcers and is linked to gastric cancer. Domestic cats from a commercial source were found to be naturally infected with H. pylori, and studies were undertaken to eradicate H. pylori from infected cats by using triple antimicrobial therapy. Eight cats infected with H. pylori were used in the study. Six cats received a 21-day course of oral amoxicillin, metronidazole, and omeprazole, and two cats served as controls. Two weeks and 4 weeks posttreatment (p.t.), all six treated cats were negative at several sites (saliva, gastric juice, and gastric mucosa) for H. pylori by culture. However, as determined by PCR with primers specific for the 26-kDa product, the majority of cats at 2 and 4 weeks p.t. had gastric fluid samples which were positive for H. pylori and three of three cats at 2 weeks p.t. had dental plaque which was positive for H. pylori. At 6 weeks p.t., all six cats had H. pylori-negative cultures for samples from several gastric sites taken at necropsy, and only one cat had H. pylori cultured from gastric juice. PCR analysis revealed that five of six cats had H. pylori DNA amplification products from plaque, saliva, and/or gastric fluid samples. Negative bacterial cultures for cats for which there was demonstrable PCR amplification of H. pylori DNA may reflect the inability of in vitro culture techniques to isolate small numbers of H. pylori organisms, focal colonization at sites not cultured, or a failure of the antibiotics to successfully eradicate H. pylori from extragastric sites which allowed subsequent recolonization of the stomach after cessation of therapy. Alternatively, the treatment strategy may have induced in vivo viable but nonculturable coccoid forms of H. pylori. The H. pylori cat model should allow further studies to test these hypotheses as well as the efficacies of other combined therapeutic regimens. Also, because 100% of these cats were naturally infected with H.pylori, this model should

  7. Infecciones por helicobacter pylori Helicobacter pylori infections

    Directory of Open Access Journals (Sweden)

    Liliam Alvarez Gil

    1994-02-01

    Full Text Available

    Se revisan los conocimientos sobre el papel de Helicobacter pylori en varias enfermedades gastroduodenales como la gastritis crónica (GC, úlcera gástrica (UG, úlcera duodenal (UD y dispepsia no ulcerosa (DNU. La revisión abarca aspectos históricos, microbiológicos, clínicos, epidemiológicos, diagnósticos de laboratorio, terapéuticos y de patogénesis.

    The current knowledge of the role of Helicobacter Pylori in several gastroduodenal  diseases is reviewed. It includes chronic gastritis, gastric and duodenal ulcers and nonulcerous dyspepsia. The following aspects are treated in this paper: history, microbiology. Clinical presentation, epidemiology, laboratory diagnosis, therapy and pathogenesis.

  8. Exopolysaccharide production by Helicobacter pylori

    OpenAIRE

    2006-01-01

    Helicobacter pylori is a widespread Gram-negative bacterium that infects the stomach of humans leading to the onset of several gastric disorders, such as, gastritis, gastric ulcers, and cancers. Studies from developing countries with low socioeconomic status and poor management of the drinking water suggest that it may serve as an environmental reservoir of H. pylori and therefore contribute to human infection. It has been reported that H. pylori has the ability to form microbi...

  9. In Vivo Accumulation of Helicobacter pylori Products, NOD1, Ubiquitinated Proteins and Proteasome in a Novel Cytoplasmic Structure

    OpenAIRE

    2010-01-01

    Cell internalization and intracellular fate of H. pylori products/virulence factors in vivo by human gastric epithelium, the main target of H. pylori-induced pathologies (i.e., peptic ulcer and cancer), are still largely unknown. Investigating gastric endoscopic biopsies from dyspeptic patients by means of ultrastructural immunocytochemistry, here we show that, in human superficial-foveolar epithelium and its metaplastic or dysplastic foci, H. pylori virulence factors accumulated in a discret...

  10. Helicobacter pylori Infection Induces Anemia, Depletes Serum Iron Storage, and Alters Local Iron-Related and Adult Brain Gene Expression in Male INS-GAS Mice.

    Science.gov (United States)

    Burns, Monika; Muthupalani, Sureshkumar; Ge, Zhongming; Wang, Timothy C; Bakthavatchalu, Vasudevan; Cunningham, Catriona; Ennis, Kathleen; Georgieff, Michael; Fox, James G

    2015-01-01

    Iron deficiency anemia (IDA) affects > 500 million people worldwide, and is linked to impaired cognitive development and function in children. Helicobacter pylori, a class 1 carcinogen, infects about half of the world's population, thus creating a high likelihood of overlapping risk. This study determined the effect of H. pylori infection on iron homeostasis in INS-GAS mice. Two replicates of INS-GAS/FVB male mice (n = 9-12/group) were dosed with H. pylori (Hp) strain SS1 or sham dosed at 6-9 weeks of age, and were necropsied at 27-29 weeks of age. Hematologic and serum iron parameters were evaluated, as was gene expression in gastric and brain tissues. Serum ferritin was lower in Hp SS1-infected mice than uninfected mice (p in mice infected with Hp SS1 compared to sham-dosed controls (pin gastric tissue of Hp SS1-infected mice (pin myelination (myelin basic protein (Mbp) and proteolipid protein 2 (Plp2)) was downregulated in infected mice (p = 0.001 and p = 0.02). Expression of synaptic plasticity markers (brain derived neurotrophic factor 3 (Bdnf3), Psd95 (a membrane associated guanylate kinase), and insulin-like growth factor 1 (Igf1)) was also downregulated in Hp SS1-infected mice (p = 0.09, p = 0.04, p = 0.02 respectively). Infection of male INS-GAS mice with Hp SS1, without concurrent dietary iron deficiency, depleted serum ferritin, deregulated gastric and hepatic expression of iron regulatory genes, and altered iron-dependent neural processes. The use of Hp SS1-infected INS-GAS mice will be an appropriate animal model for further study of the effects of concurrent H. pylori infection and anemia on iron homeostasis and adult iron-dependent brain gene expression.

  11. NikR mediates nickel-responsive transcriptional induction of urease expression in Helicobacter pylori.

    Science.gov (United States)

    van Vliet, Arnoud H M; Poppelaars, Sophie W; Davies, Beverly J; Stoof, Jeroen; Bereswill, Stefan; Kist, Manfred; Penn, Charles W; Kuipers, Ernst J; Kusters, Johannes G

    2002-06-01

    The important human pathogen Helicobacter pylori requires the abundant expression and activity of its urease enzyme for colonization of the gastric mucosa. The transcription, expression, and activity of H. pylori urease were previously demonstrated to be induced by nickel supplementation of growth media. Here it is demonstrated that the HP1338 protein, an ortholog of the Escherichia coli nickel regulatory protein NikR, mediates nickel-responsive induction of urease expression in H. pylori. Mutation of the HP1338 gene (nikR) of H. pylori strain 26695 resulted in significant growth inhibition of the nikR mutant in the presence of supplementation with NiCl(2) at > or =100 microM, whereas the wild-type strain tolerated more than 10-fold-higher levels of NiCl(2). Mutation of nikR did not affect urease subunit expression or urease enzyme activity in unsupplemented growth media. However, the nickel-induced increase in urease subunit expression and urease enzyme activity observed in wild-type H. pylori was absent in the H. pylori nikR mutant. A similar lack of nickel responsiveness was observed upon removal of a 19-bp palindromic sequence in the ureA promoter, as demonstrated by using a genomic ureA::lacZ reporter gene fusion. In conclusion, the H. pylori NikR protein and a 19-bp operator sequence in the ureA promoter are both essential for nickel-responsive induction of urease expression in H. pylori.

  12. Changes in serum ammonia concentration in cirrhotic patients with Helicobacter pylori infection

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To study whether liver cirrhosis associated with Helicopacter pylori (H. pylori)infection will induce increased serum ammonia and whether the peripheral serum ammonia reflects the level of portal vein serum ammonia. Methods Blood was taken from the portal vein and the cubital vein in cirrhotic patients with and without H.pylori infection and non-cirrhotic patients (splenic rupiure) with and without H. pylori infection, and the serum ammonia was measured. Results The mean levels of serum ammonia in the group of cirrhotic patients with H. pylori infection were 167.82±8.97 μmol/L (pertal vein) and 142.2±13.35 μmol/L (cubital vein). They were increased significantly as compared with cirrhotic patients without H.pyiori infection(47.68±12.03 μmol/L portal vein and 37.23±7.04 μmol/L cubital vein),and also compared with the groups of splenic rupture patients with and without H. pylori infection (P<0.0t).There was no significant difference between the serum ammonia level of the cubital vein and pertal vein(P>0.05). Conclusions H.pylori intection can induce an increase in serum ammonia in patients with liver dysfunction,and the peripheral serum ammonia measurement may replace the portal vein serum ammania as a monitoring method. Eradication of H.pylori in cirrhotic patients may prevent hepatic encephalopathy(HE).

  13. Fragmentation of CagA Reduces Hummingbird Phenotype Induction by Helicobactor pylori.

    Directory of Open Access Journals (Sweden)

    Chih-Chi Chang

    Full Text Available Infection with Helicobacter pylori (H. pylori has been linked to various gastro-intestinal diseases; nevertheless it remains to be clarified why only a minority of infected individuals develop illness. Studies from the West have indicated that the cagA gene and the associated EPIYA genotype of H. pylori is closely linked to the development of severe gastritis and gastric carcinoma; however, as yet no consistent correlation has been found among the bacteria from East Asia. In addition to genotype variation, the CagA protein undergoes fragmentation; however, the functional significance of fragmentation with respect to H. pylori infection remains unknown. In this study, we isolated 594 H. pylori colonies from 99 patients and examined the fragmentation patterns of CagA protein using immunoblotting. By analyzing the ability of the isolates to induce the host cell morphological transition to the highly invasive hummingbird phenotype, we demonstrated that H. pylori colonies with substantial CagA fragmentation are less potent in terms of causing this morphological transition. Our results uncovered a functional role for CagA fragmentation with respect to H. pylori-induced hummingbird phenotype formation and these findings suggest the possibility that the post-translational processing of CagA may be involved in H. pylori infection pathogenesis.

  14. Role of Toll-like receptors in Helicobacter pylori infection and immunity

    Institute of Scientific and Technical Information of China (English)

    Sinéad; M; Smith

    2014-01-01

    The gram-negative bacterium Helicobacter pylori(H. pylori) infects the stomachs of approximately half of the world’s population. Although infection induces an immune response that contributes to chronic gastric inflammation, the response is not sufficient to eliminate the bacterium. H. pylori infection causes peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma. Disease outcome is linked to the severity of the host inflammatory response. Gastric epithelial cells represent the first line of innate immune defence against H. pylori, and respond to infection by initiating numerous cell signalling cascades, resulting in cytokine induction and the subsequent recruitment of inflamma-tory cells to the gastric mucosa. Pathogen recognition receptors of the toll-like receptor(TLR) family mediate many of these cell signalling events. This review dis-cusses recent findings on the role of various TLRs in the recognition of H. pylori in distinct cell types, describes the TLRs responsible for the recognition of individual H. pylori components and outlines the influence of innate immune activation on the subsequent development of the adaptive immune response. The mechanistic iden-tification of host mediators of H. pylori-induced patho-genesis has the potential to reveal drug targets and opportunities for therapeutic intervention or prevention of H. pylori-associated disease by means of vaccines or immunomodulatory therapy.

  15. Induction of CD69 expression by cagPAI-positive Helicobacter pylori infection

    Institute of Scientific and Technical Information of China (English)

    Naoki Mori; Chie Ishikawa; Masachika Senba

    2011-01-01

    AIM: To investigate and elucidate the molecular mech-anism that regulates inducible expression of CD69 by Helicobacter pylori (H. pylori ) infection.METHODS: The expression levels of CD69 in a T-cell line, Jurkat, primary human peripheral blood mononu-clear cells (PBMCs), and CD4+T cells, were assessed by immunohistochemistry, reverse transcription polymerase chain reaction, and flow cytometry. Activation of CD69 promoter was detected by reporter gene. Nuclear factor (NF)-κB activation in Jurkat cells infected with H. pylori was evaluated by electrophoretic mobility shift assay. The role of NF-κB signaling in H. pylori -induced CD69 expression was analyzed using inhibitors of NF-κB and dominant-negative mutants. The isogenic mutants with disrupted cag pathogenicity island ( cagPAI) and virD4 were used to elucidate the role of cagPAI-encoding type Ⅳ secretion system and CagA in CD69 expression.RESULTS: CD69 staining was detected in mucosal lymphocytes and macrophages in specimens of pa-tients with H. pylori -positive gastritis. Although cagPAI-positive H. pylori and an isogenic mutant of virD4 induced CD69 expression, an isogenic mutant of cag-PAI failed to induce this in Jurkat cells. H. pylori also induced CD69 expression in PBMCs and CD4+T cells. The activation of the CD69 promoter by H. pylori was mediated through NF-κB. Transfection of dominant-negative mutants of IκBs, IκB kinases, and NF-κB-inducing kinase inhibited H. pylori -induced CD69 activation. Inhibitors of NF-κB suppressed H. pylori -induced CD69 mRNA expression.CONCLUSION: The results suggest that H. pylori in-duces CD69 expression through the activation of NF-κB. cagPAI might be relevant in the induction of CD69 expression in T cells. CD69 in T cells may play a role in H. pylori -induced gastritis.

  16. Helicobacter pylori in Iran: A systematic review on the association of genotypes and gastroduodenal diseases

    Science.gov (United States)

    Hosseini, Elham; Poursina, Farkhondeh; de Wiele, Tom Van; Safaei, Hajieh Ghasemian; Adibi, Peyman

    2012-01-01

    Background: Helicobacter pylori (H. pylori) infection is known as a major etiologic factor for a variety of gastroduodenal diseases. In Iran, with a high rate of H. pylori infection close to 90%, numerous studies have revealed many aspects of interaction between the bacterium, mucosal surface and induction of disease outcome. The organism is genetically diverse and several virulence factors are attributed to the more virulent strains. The well-characterized virulence factors of H. pylori are cytotoxin associated gene A and vacuolating cytotoxin gene A. The distribution pattern of H. pylori genotypes and its association with disease status varies geographically. The present review focused on the virulence factors and genotyping of H. pylori in relation to gastroduodenal disorders in different regions of Iran. Methods: In total, 398 studies were reported on different aspects related to H. pylori in our electronic search from 1995-2011. H. pylori infection and its virulence factors in association with disease status were investigated in 159 reports. Looking specifically at the gastrointestinal tract disorders, the most relevant reports including 37 papers were selected. Results: We found no correlation of cagA genotype and disease status in the majority of studies, whereas vacA was demonstrated as a useful marker in predicting the disease outcome. The results of reports on other virulence factors of H. pylori such as blood group antigen-binding adhesion gene A, the induced by contact with epithelium gene A, the outer inflammatory protein A, the duodenal ulcer promoting gene A, and Helicobacter outer membrane gene and their relation with disease status were contradictory. Conclusions: Although different markers of H. pylori were emphasized as useful when predicting disease outcomes in some studies, the inconsistent researches and the scarcity of data made any conclusion or even comparison impossible. Considering the gap of information observed during our search

  17. Inactivation of Helicobacter pylori by Chloramination

    Science.gov (United States)

    Three strains of Helicobacter pylori (H. pylori) were studied to determine their resistance to chloramination. H. pylori is an organism listed on the U.S. Environmental Protection Agency’s (USEPA) Contaminant Control List (CCL). H. pylori was exposed to 2ppm of pre-formed monoc...

  18. Inactivation of Helicobacter pylori by Chloramination

    Science.gov (United States)

    Three strains of Helicobacter pylori (H. pylori) were studied to determine their resistance to chloramination. H. pylori is an organism listed on the U.S. Environmental Protection Agency’s (USEPA) Contaminant Control List (CCL). H. pylori was exposed to 2ppm of pre-formed monoc...

  19. Halitosis and Helicobacter pylori infection.

    Science.gov (United States)

    Tangerman, A; Winkel, E G; de Laat, L; van Oijen, A H; de Boer, W A

    2012-03-01

    There is disagreement about a possible relationship between Helicobacter pylori (H. pylori) infection and objective halitosis, as established by volatile sulfur compounds (VSCs) in the breath. Many studies related to H. pylori used self-reported halitosis, a subjective and unreliable method to detect halitosis. In this study a possible relation between H. pylori and halitosis was evaluated, using an objective method (gas chromatography, GC) to detect the VSCs, responsible for the halitosis. The levels of the VSCs hydrogen sulfide (H(2)S), methyl mercaptan (MM) and dimethyl sulfide (DMS) were measured in mouth breath and in stomach air of 11 H. pylori positive patients and of 38 H. pylori negative patients, all with gastric pathology. Halitosis was also established by organoleptic scoring (OLS) of mouth-breath. The levels of H(2)S, MM and DMS in the mouth-breath and stomach air of the H. pylori positive patients did not differ significantly from those of the H. pylori negative patients. OLS of the mouth-breath resulted in 9 patients with halitosis, 1 out of the H. pylori positive group and 8 out of the H. pylori negative group, which is not statistically different. The concentrations of the VSCs in stomach air were in nearly all cases below the thresholds of objectionability of the various VSCs, indicating that halitosis does not originate in the stomach. The patients with gastric pathology were also compared with control patients without gastric pathology and with normal volunteers. No significant differences in VSCs in mouth breath were observed between these groups. Thus, in this study no association between halitosis and H. pylori infection was found. Halitosis, as established by GC and OLS, nearly always originates within the oral cavity and seldom or never within the stomach.

  20. Effects of Helicobacter pylori and Heat Shock Protein 70 on the Proliferation of Human Gastric Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Liping Tao

    2014-01-01

    Full Text Available Infection of Helicobacter pylori (H. pylori changed the proliferation of gastric epithelial cells and decreased the expression of heat shock protein 70 (HSP70. However, the effects of H. pylori on the proliferation of gastric epithelial cells and the roles of HSP70 during the progress need further investigation. Objective. To investigate the effects of Helicobacter pylori (H. pylori and heat shock protein 70 (HSP70 on the proliferation of human gastric epithelial cells. Methods. H. pylori and a human gastric epithelial cell line (AGS were cocultured. The proliferation of AGS cells was quantitated by an MTT assay, and the expression of HSP70 in AGS cells was detected by Western blotting. HSP70 expression in AGS cells was silenced by small interfering RNA (siRNA to investigate the role of HSP70. The siRNA-treated AGS cells were cocultured with H. pylori and cell proliferation was measured by an MTT assay. Results. The proliferation of AGS cells was accelerated by coculturing with H. pylori for 4 and 8 h, but was suppressed at 24 and 48 h. HSP70 expression was decreased in AGS cells infected by H. pylori for 48 h. The proliferation in HSP70-silenced AGS cells was inhibited after coculturing with H. pylori for 24 and 48 h compared with the control group. Conclusions. Coculture of H. pylori altered the proliferation of gastric epithelial cells and decreased HSP70 expression. HSP70 knockdown supplemented the inhibitory effect of H. pylori on proliferation of epithelial cells. These results indicate that the effects of H. pylori on the proliferation of gastric epithelial cells at least partially depend on the decreased expression of HSP70 induced by the bacterium.

  1. In situ targeted MRI detection of Helicobacter pylori with stable magnetic graphitic nanocapsules

    Science.gov (United States)

    Li, Yunjie; Hu, Xiaoxiao; Ding, Ding; Zou, Yuxiu; Xu, Yiting; Wang, Xuewei; Zhang, Yin; Chen, Long; Chen, Zhuo; Tan, Weihong

    2017-06-01

    Helicobacter pylori infection is implicated in the aetiology of many diseases. Despite numerous studies, a painless, fast and direct method for the in situ detection of H. pylori remains a challenge, mainly due to the strong acidic/enzymatic environment of the gastric mucosa. Herein, we report the use of stable magnetic graphitic nanocapsules (MGNs), for in situ targeted magnetic resonance imaging (MRI) detection of H. pylori. Several layers of graphene as the shell effectively protect the magnetic core from corrosion while retaining the superior contrast effect for MRI in the gastric environment. Boronic-polyethylene glycol molecules were synthesized and modified on the MGN surface for targeted MRI detection. In a mouse model of H. pylori-induced infection, H. pylori was specifically detected through both T2-weighted MR imaging and Raman gastric mucosa imaging using functionalized MGNs. These results indicated that enhancement of MRI using MGNs may be a promising diagnostic and bioimaging platform for very harsh conditions.

  2. Helicobacter pylori infection

    Institute of Scientific and Technical Information of China (English)

    Yvan Vandenplas

    2000-01-01

    @@ IS THERE ANYTHING NEW? Helicobacter pylori has been for many years a forgotten bacterium, since the first report on this spiral organism dated from the 19th century[1]. As early as in 1906, an association between a spiral organism and gastric carcinoma was suggested[2].Doenges reported in 1938 that on autopsy not less than 40% of human stomachs were found to be invaded by spiral organisms[3].

  3. Nitroimidazole resistance in Helicobacter pylori

    NARCIS (Netherlands)

    Van der Wouden, EJ; Thijs, JC; Van Zwet, AA; Kleibeuker, JH

    2000-01-01

    The efficacy of a nitroimidazole-containing regimen for the treatment of Helicobacter pylori infection is decreased by nitroimidazole resistance. Nitroimidazoles are metabolized by H. pylori by several nitro-reductases of which an oxygen-insensitive NADPH nitroreductase encoded by the rdxA gene is t

  4. Helicobacter pylori infection in pediatrics

    DEFF Research Database (Denmark)

    Wewer, Anne Vibeke; Kalach, Nicolas

    2003-01-01

    in gastric manifestations is the subject of conflicting reports. Extra-digestive manifestations are also reported in the course of this infection. The treatment of H. pylori infection is influenced by resistance of the bacteria to the antibiotics used. We suggest that eradication of H. pylori should take...

  5. Pathogenesis of Helicobacter pylori infection

    NARCIS (Netherlands)

    J.G. Kusters (Johannes); A.H.M. van Vliet (Arnoud); E.J. Kuipers (Ernst)

    2006-01-01

    textabstractHelicobacter pylori is the first formally recognized bacterial carcinogen and is one of the most successful human pathogens, as over half of the world's population is colonized with this gram-negative bacterium. Unless treated, colonization usually persists lifelong. H. pylori infection

  6. Epidemiology of Helicobacter pylori infection.

    Science.gov (United States)

    Eusebi, Leonardo H; Zagari, Rocco M; Bazzoli, Franco

    2014-09-01

    Medline and PubMed databases were searched on epidemiology of Helicobacter pylori for the period of April 2013-March 2014. Several studies have shown that the prevalence of H. pylori is still high in most countries. In north European and North American populations, about one-third of adults are still infected, whereas in south and east Europe, South America, and Asia, the prevalence of H. pylori is often higher than 50%. H. pylori remains highly prevalent in immigrants coming from countries with high prevalence of H. pylori. However, the lower prevalence of infection in the younger generations suggests a further decline of H. pylori prevalence in the coming decades. Low socioeconomic conditions in childhood are confirmed to be the most important risk factors for H. pylori infection. Although the way the infection is transmitted is still unclear, interpersonal transmission appears to be the main route. Finally, H. pylori recurrence after successful eradication can still occur, but seems to be an infrequent event.

  7. Interleukin-17C in Human Helicobacter pylori Gastritis.

    Science.gov (United States)

    Tanaka, Shingo; Nagashima, Hiroyuki; Cruz, Modesto; Uchida, Tomohisa; Uotani, Takahiro; Jiménez Abreu, José A; Mahachai, Varocha; Vilaichone, Ratha-Korn; Ratanachu-Ek, Thawee; Tshering, Lotay; Graham, David Y; Yamaoka, Yoshio

    2017-10-01

    The interleukin-17 (IL-17) family of cytokines (IL-17A to IL-17F) is involved in many inflammatory diseases. Although IL-17A is recognized as being involved in the pathophysiology of Helicobacter pylori-associated diseases, the role of other IL-17 cytokine family members remains unclear. Microarray analysis of IL-17 family cytokines was performed in H. pylori-infected and uninfected gastric biopsy specimens. IL-17C mRNA was upregulated approximately 4.5-fold in H. pylori-infected gastric biopsy specimens. This was confirmed by quantitative reverse transcriptase PCR in infected and uninfected gastric mucosa obtained from Bhutan and from the Dominican Republic. Immunohistochemical analysis showed that IL-17C expression in H. pylori-infected gastric biopsy specimens was predominantly localized to epithelial and chromogranin A-positive endocrine cells. IL-17C mRNA levels were also significantly greater among cagA-positive than cagA-negative H. pylori infections (P = 0.012). In vitro studies confirmed an increase in IL-17C mRNA and protein levels in cells infected with cagA-positive infections compared to cells infected with either cagA-negative or cag pathogenicity island (PAI) mutant. Chemical inhibition of IκB kinase (IKK), mitogen-activated protein extracellular signal-regulated kinase (MEK), and Jun N-terminal kinase (JNK) inhibited induction of IL-17C proteins in infected cells, whereas p38 inhibition had no effect on IL-17C protein secretion. In conclusion, H. pylori infection was associated with a significant increase in IL-17C expression in human gastric mucosa. The role of IL-17C in the pathogenesis of H. pylori-induced diseases remains to be determined. Copyright © 2017 American Society for Microbiology.

  8. Does Helicobacter pylori play a role in the pathogenesis of childhood chronic idiopathic thrombocytopenic purpura?

    Directory of Open Access Journals (Sweden)

    Maryam Maghbool

    2009-07-01

    Full Text Available Idiopathic thrombocytopenic purpura (ITP is an acute self-limited bleeding disorder that can progress to chronic form in 10-15% of the cases. Helicobacter pylori (H. pylori infection is a possible cause of chronic ITP. We studied 30 children with resistant chronic ITP for H. pylori infection based on the detection of H. pylori fecal antigen. This retrospective study was based on data obtained from medical records of 30 children aged between five and 17 years (median age at ITP diagnosis was ten years. A specially-designed data sheet was used to record information on age, sex, duration of disease, family history of bleeding disorders, previous treatments and median platelet count. In patients with H. pylori infection, antimicrobial treatment consisted of amoxicillin, metronidazol and omeprazol. Response was assessed every month for one year and defined as complete (platelet count >150x109/L or partial (platelet count between 50 and 150x109/L. We detected H. pylori infection in 5 patients. In 4 of them increased platelet count was seen during one year of follow-up and in one patient the platelet count was acceptable during six months. Although the pathological mechanism of H. pylori-induced thrombocytopenia was unclear in our patient sample, the assessment of H. pylori infection and use of eradication therapy should be attempted in chronic and resistant ITP patients.

  9. Does Helicobacter pylori play a role in the pathogenesis of childhood chronic idiopathic thrombocytopenic purpura?

    Science.gov (United States)

    Maghbool, Maryam; Maghbool, Masood; Shahriari, Mehdi; Karimi, Mehran

    2009-06-08

    Idiopathic thrombocytopenic purpura (ITP) is an acute self-limited bleeding disorder that can progress to chronic form in 10-15% of the cases. Helicobacter pylori (H. pylori) infection is a possible cause of chronic ITP. We studied 30 children with resistant chronic ITP for H. pylori infection based on the detection of H. pylori fecal antigen. This retrospective study was based on data obtained from medical records of 30 children aged between five and 17 years (median age at ITP diagnosis was ten years). A specially-designed data sheet was used to record information on age, sex, duration of disease, family history of bleeding disorders, previous treatments and median platelet count. In patients with H. pylori infection, antimicrobial treatment consisted of amoxicillin, metronidazol and omeprazol. Response was assessed every month for one year and defined as complete (platelet count >150×10(9)/L) or partial (platelet count between 50 and 150×10(9)/L). We detected H. pylori infection in 5 patients. In 4 of them increased platelet count was seen during one year of follow-up and in one patient the platelet count was acceptable during six months. Although the pathological mechanism of H. pylori-induced thrombocytopenia was unclear in our patient sample, the assessment of H. pylori infection and use of eradication therapy should be attempted in chronic and resistant ITP patients.

  10. From the stomach to other organs: Helicobacter pylori and the liver

    Institute of Scientific and Technical Information of China (English)

    Marek; Waluga; Micha?; Kukla; Micha?; ?orniak; Agata; Bacik; Rafa?; Kotulski

    2015-01-01

    Many recent studies have examined the importance of Helicobacter pylori(H. pylori) infection in the pathogenesis of the diseases outside the stomach and explored the significance of this bacterium in the pathogenesis of some metabolic and cardiovascular diseases. Recent studies have provided evidence that H. pylori is also involved in the pathogenesis of some liver diseases. Many observations have proved that H. pylori infection is important in the development of insulin resistance, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, liver fibrosis and cirrhosis. The worsening of liver inflammation of different origins also occurs during H. pylori infection. Some studies have indicated that H. pylori infection induces autoimmunological diseases in the liver and biliary tract. The potential significance of this bacterium in carcinogenesis is unclear, but it is within the scope of interest of many studies. The proposed mechanisms through which H. pylori impacts the development of hepatobiliary diseases are complex and ambiguous. The importance of other Helicobacter species in the development of hepatobiliary diseases is also considered because they could lead to the development of inflammatory, fibrotic and necrotic injuries of the liver and, consequently, to hepatocellular carcinoma. However, many contrary viewpoints indicate that some evidence is not convincing, and further studies of the subject are needed. This review presents the current knowledge about the importance of H. pylori in the pathogenesis of liver and in biliary diseases.

  11. Genetic determinants and clinico-pathological outcomes of helicobacter pylori infection.

    Science.gov (United States)

    Oluwasola, A O

    2014-06-01

    Helicobacter pylori is a spiral Gram-negative bacterium with a relatively small genome and is known to be the most common human bacterial infection worldwide, infecting about half of the world's population. The bacterium represents one of the most successful human pathogens, inducing severe clinical symptoms only in a small subset of individuals, thus signifying a highly balanced degree of co-evolution of H. pylori and humans. The prevalence of Helicobacter pylori infection varies greatly among countries and among population groups within the same country, but is falling in most developed countries. The clinical course of H. pylori infection is highly variable and is influenced by both microbial and host factors including genetic susceptibility while the pattern and distribution of inflammation correlate strongly with the risk of clinical sequelae, namely duodenal or gastric ulcers, mucosal atrophy, gastric carcinoma, or gastric lymphoma. Cytokine gene polymorphisms directly influence inter-individual variation in the magnitude of cytokine response, and this clearly contributes to an individual's ultimate clinical outcome. Polymorphisms in genes coding for innate immune factors have also been incriminated in the pathogenesis of H. pylori related disease, while promoter hypermethylation of tumor suppressor genes is considered an important factor in carcinogenesis and known to be present in H. pylori associated gastric tumors. Functional genomics may fill many of the gaps in our understanding of the pathogenesis of H. pylori infection and accelerate the development of novel therapies, including H. pylori specific antimicrobial agents.

  12. Myeloid HIF-1 is protective in Helicobacter pylori-mediated gastritis.

    Science.gov (United States)

    Matak, Pavle; Heinis, Mylène; Mathieu, Jacques R R; Corriden, Ross; Cuvellier, Sylvain; Delga, Stéphanie; Mounier, Rémi; Rouquette, Alexandre; Raymond, Josette; Lamarque, Dominique; Emile, Jean-François; Nizet, Victor; Touati, Eliette; Peyssonnaux, Carole

    2015-04-01

    Helicobacter pylori infection triggers chronic inflammation of the gastric mucosa that may progress to gastric cancer. The hypoxia-inducible factors (HIFs) are the central mediators of cellular adaptation to low oxygen levels (hypoxia), but they have emerged recently as major transcriptional regulators of immunity and inflammation. No studies have investigated whether H. pylori affects HIF signaling in immune cells and a potential role for HIF in H. pylori-mediated gastritis. HIF-1 and HIF-2 expression was examined in human H. pylori-positive gastritis biopsies. Subsequent experiments were performed in naive and polarized bone marrow-derived macrophages from wild-type (WT) and myeloid HIF-1α-null mice (HIF-1(Δmyel)). WT and HIF-1(Δmyel) mice were inoculated with H. pylori by oral gavage and sacrificed 6 mo postinfection. HIF-1 was specifically expressed in macrophages of human H. pylori-positive gastritis biopsies. Macrophage HIF-1 strongly contributed to the induction of proinflammatory genes (IL-6, IL-1β) and inducible NO synthase in response to H. pylori. HIF-2 expression and markers of M2 macrophage differentiation were decreased in response to H. pylori. HIF-1(Δmyel) mice inoculated with H. pylori for 6 mo presented with a similar bacterial colonization than WT mice but, surprisingly, a global increase of inflammation, leading to a worsening of the gastritis, measured by an increased epithelial cell proliferation. In conclusion, myeloid HIF-1 is protective in H. pylori-mediated gastritis, pointing to the complex counterbalancing roles of innate immune and inflammatory phenotypes in driving this pathology. Copyright © 2015 by The American Association of Immunologists, Inc.

  13. Helicobacter pylori Activates HMGB1 Expression and Recruits RAGE into Lipid Rafts to Promote Inflammation in Gastric Epithelial Cells

    Science.gov (United States)

    Lin, Hwai-Jeng; Hsu, Fang-Yu; Chen, Wei-Wei; Lee, Che-Hsin; Lin, Ying-Ju; Chen, Yi-Ywan M.; Chen, Chih-Jung; Huang, Mei-Zi; Kao, Min-Chuan; Chen, Yu-An; Lai, Hsin-Chih; Lai, Chih-Ho

    2016-01-01

    Helicobacter pylori infection is associated with several gastrointestinal disorders in the human population worldwide. High-mobility group box 1 (HMGB1), a ubiquitous nuclear protein, mediates various inflammation functions. The interaction between HMGB1 and receptor for advanced glycation end-products (RAGE) triggers nuclear factor (NF)-κB expression, which in turn stimulates the release of proinflammatory cytokines, such as interleukin (IL)-8, and enhances the inflammatory response. However, how H. pylori activates HMGB1 expression and mobilizes RAGE into cholesterol-rich microdomains in gastric epithelial cells to promote inflammation has not been explored. In this study, we found that HMGB1 and RAGE expression increased significantly in H. pylori-infected cells compared with -uninfected cells. Blocking HMGB1 by neutralizing antibody abrogated H. pylori-elicited RAGE, suggesting that RAGE expression follows HMGB1 production, and silenced RAGE-attenuated H. pylori-mediated NF-κB activation and IL-8 production. Furthermore, significantly more RAGE was present in detergent-resistant membranes extracted from H. pylori-infected cells than in those from -uninfected cells, indicating that H. pylori exploited cholesterol to induce the HMGB1 signaling pathway. These results indicate that HMGB1 plays a crucial role in H. pylori-induced inflammation in gastric epithelial cells, which may be valuable in developing treatments for H. pylori-associated diseases. PMID:27667993

  14. Annexin A4: A novel molecular marker for gastric cancer with Helicobacter pylori infection using proteomics approach.

    Science.gov (United States)

    Lin, Li-Ling; Chen, Chiung-Nien; Lin, Wei-Chou; Lee, Po-Huang; Chang, King-Jen; Lai, Yo-Ping; Wang, Jin-Town; Juan, Hsueh-Fen

    2008-04-01

    Helicobacter pylori was reported to be an important risk factor for the carcinogenesis of gastric cancer. Here, we used a proteomic approach to find differentially expressed proteins between the normal and tumor tissue of gastric cancer patients infected with H. pylori. In our results, we found annexin A4 was over-expressed in patients infected with H. pylori and was found in tumor cells, and over-expressed in gastric cancer SCM-1 cells after H. pylori infection. Ca(2+ ) can be induced by H. pylori and interact with annexin A4 Ca(2+) binding site to block the calmodulin-activated chloride conductance activation; therefore, it produces a new environment that benefits the malignant existence of H. pylori and raises the risk for gastric cancer. We also found interleuken-8 (IL-8) expression levels were increased in H. pylori infected SCM-1 cells. Combined with previous reports and our results, we summarize that the over-expression of annexin A4 in SCM-1 cells with H. pylori infection may subsequently induce IL-8 which can further cause tumor angiogenesis. In this paper, we show that annexin A4 is a potential novel molecular marker for gastric cancer with H. pylori infection, and our results may provide a new insight in the development of new anti-cancer drugs. Copyright © 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Helicobacter pylori Activates HMGB1 Expression and Recruits RAGE into Lipid Rafts to Promote Inflammation in Gastric Epithelial Cells.

    Science.gov (United States)

    Lin, Hwai-Jeng; Hsu, Fang-Yu; Chen, Wei-Wei; Lee, Che-Hsin; Lin, Ying-Ju; Chen, Yi-Ywan M; Chen, Chih-Jung; Huang, Mei-Zi; Kao, Min-Chuan; Chen, Yu-An; Lai, Hsin-Chih; Lai, Chih-Ho

    2016-01-01

    Helicobacter pylori infection is associated with several gastrointestinal disorders in the human population worldwide. High-mobility group box 1 (HMGB1), a ubiquitous nuclear protein, mediates various inflammation functions. The interaction between HMGB1 and receptor for advanced glycation end-products (RAGE) triggers nuclear factor (NF)-κB expression, which in turn stimulates the release of proinflammatory cytokines, such as interleukin (IL)-8, and enhances the inflammatory response. However, how H. pylori activates HMGB1 expression and mobilizes RAGE into cholesterol-rich microdomains in gastric epithelial cells to promote inflammation has not been explored. In this study, we found that HMGB1 and RAGE expression increased significantly in H. pylori-infected cells compared with -uninfected cells. Blocking HMGB1 by neutralizing antibody abrogated H. pylori-elicited RAGE, suggesting that RAGE expression follows HMGB1 production, and silenced RAGE-attenuated H. pylori-mediated NF-κB activation and IL-8 production. Furthermore, significantly more RAGE was present in detergent-resistant membranes extracted from H. pylori-infected cells than in those from -uninfected cells, indicating that H. pylori exploited cholesterol to induce the HMGB1 signaling pathway. These results indicate that HMGB1 plays a crucial role in H. pylori-induced inflammation in gastric epithelial cells, which may be valuable in developing treatments for H. pylori-associated diseases.

  16. Mutagenicity and clastogenicity of extracts of Helicobacter pylori detected by the Ames test and in the micronucleus test using human lymphoblastoid cells.

    Science.gov (United States)

    Arimoto-Kobayashi, Sakae; Ohta, Kaori; Yuhara, Yuta; Ayabe, Yuka; Negishi, Tomoe; Okamoto, Keinosuke; Nakajima, Yoshihiro; Ishikawa, Takeshi; Oguma, Keiji; Otsuka, Takanao

    2015-07-01

    Epidemiological studies have demonstrated a close association between infection with Helicobacter pylori (H.pylori) and the development of gastric carcinoma. Chronic H.pylori infection increases the frequency of mutation in gastric epithelial cells. However, the mechanism by which infection of H.pylori leads to mutation in gastric epithelial cells is unclear. We suspected that components in H.pylori may be related to the mutagenic response associated with DNA alkylation, and could be detected with the Ames test using a more sensitive strain for alkylating agents. Our investigation revealed that an extract of H.pylori was mutagenic in the Ames test with Salmonella typhimurium YG7108, which is deficient in the DNA repair of O(6)-methylguanine. The extract of H.pylori may contain methylating or alkylating agents, which might induce O (6)-alkylguanine in DNA. Mutagenicity of the alkylating agents N-methyl-N-nitrosourea (MNU) and N-methyl-N'-nitro-N-nitrosoguanidine in the Ames test with S.typhimurium TA1535 was enhanced significantly in the presence of the extract of H.pylori. The tested extracts of H.pylori resulted in a significant induction of micronuclei in human-derived lymphoblastoid cells. Heat instability and dialysis resistance of the extracts of H.pylori suggest that the mutagenic component in the extracts of H.pylori is a heat-unstable large molecule or a heat-labile small molecule strongly attached or adsorbed to a large molecule. Proteins in the extracts of H.pylori were subsequently fractionated using ammonium sulphate precipitation. However, all fractions expressed enhancing effects toward MNU mutagenicity. These results suggest the mutagenic component is a small molecule that is absorbed into proteins in the extract of H.pylori, which resist dialysis. Continuous and chronic exposure of gastric epithelial cells to the alkylative mutagenic component from H.pylori chronically infected in the stomach might be a causal factor in the gastric carcinogenesis

  17. Caveolin-1 Protects B6129 Mice against Helicobacter pylori Gastritis

    Science.gov (United States)

    Hitkova, Ivana; Yuan, Gang; Anderl, Florian; Gerhard, Markus; Kirchner, Thomas; Reu, Simone; Röcken, Christoph; Schäfer, Claus; Schmid, Roland M.; Vogelmann, Roger; Ebert, Matthias P. A.; Burgermeister, Elke

    2013-01-01

    Caveolin-1 (Cav1) is a scaffold protein and pathogen receptor in the mucosa of the gastrointestinal tract. Chronic infection of gastric epithelial cells by Helicobacter pylori (H. pylori) is a major risk factor for human gastric cancer (GC) where Cav1 is frequently down-regulated. However, the function of Cav1 in H. pylori infection and pathogenesis of GC remained unknown. We show here that Cav1-deficient mice, infected for 11 months with the CagA-delivery deficient H. pylori strain SS1, developed more severe gastritis and tissue damage, including loss of parietal cells and foveolar hyperplasia, and displayed lower colonisation of the gastric mucosa than wild-type B6129 littermates. Cav1-null mice showed enhanced infiltration of macrophages and B-cells and secretion of chemokines (RANTES) but had reduced levels of CD25+ regulatory T-cells. Cav1-deficient human GC cells (AGS), infected with the CagA-delivery proficient H. pylori strain G27, were more sensitive to CagA-related cytoskeletal stress morphologies (“humming bird”) compared to AGS cells stably transfected with Cav1 (AGS/Cav1). Infection of AGS/Cav1 cells triggered the recruitment of p120 RhoGTPase-activating protein/deleted in liver cancer-1 (p120RhoGAP/DLC1) to Cav1 and counteracted CagA-induced cytoskeletal rearrangements. In human GC cell lines (MKN45, N87) and mouse stomach tissue, H. pylori down-regulated endogenous expression of Cav1 independently of CagA. Mechanistically, H. pylori activated sterol-responsive element-binding protein-1 (SREBP1) to repress transcription of the human Cav1 gene from sterol-responsive elements (SREs) in the proximal Cav1 promoter. These data suggested a protective role of Cav1 against H. pylori-induced inflammation and tissue damage. We propose that H. pylori exploits down-regulation of Cav1 to subvert the host's immune response and to promote signalling of its virulence factors in host cells. PMID:23592983

  18. Caveolin-1 protects B6129 mice against Helicobacter pylori gastritis.

    Directory of Open Access Journals (Sweden)

    Ivana Hitkova

    Full Text Available Caveolin-1 (Cav1 is a scaffold protein and pathogen receptor in the mucosa of the gastrointestinal tract. Chronic infection of gastric epithelial cells by Helicobacter pylori (H. pylori is a major risk factor for human gastric cancer (GC where Cav1 is frequently down-regulated. However, the function of Cav1 in H. pylori infection and pathogenesis of GC remained unknown. We show here that Cav1-deficient mice, infected for 11 months with the CagA-delivery deficient H. pylori strain SS1, developed more severe gastritis and tissue damage, including loss of parietal cells and foveolar hyperplasia, and displayed lower colonisation of the gastric mucosa than wild-type B6129 littermates. Cav1-null mice showed enhanced infiltration of macrophages and B-cells and secretion of chemokines (RANTES but had reduced levels of CD25+ regulatory T-cells. Cav1-deficient human GC cells (AGS, infected with the CagA-delivery proficient H. pylori strain G27, were more sensitive to CagA-related cytoskeletal stress morphologies ("humming bird" compared to AGS cells stably transfected with Cav1 (AGS/Cav1. Infection of AGS/Cav1 cells triggered the recruitment of p120 RhoGTPase-activating protein/deleted in liver cancer-1 (p120RhoGAP/DLC1 to Cav1 and counteracted CagA-induced cytoskeletal rearrangements. In human GC cell lines (MKN45, N87 and mouse stomach tissue, H. pylori down-regulated endogenous expression of Cav1 independently of CagA. Mechanistically, H. pylori activated sterol-responsive element-binding protein-1 (SREBP1 to repress transcription of the human Cav1 gene from sterol-responsive elements (SREs in the proximal Cav1 promoter. These data suggested a protective role of Cav1 against H. pylori-induced inflammation and tissue damage. We propose that H. pylori exploits down-regulation of Cav1 to subvert the host's immune response and to promote signalling of its virulence factors in host cells.

  19. Helicobacter pylori in gastroduodenal perforation

    Directory of Open Access Journals (Sweden)

    Bharat B Dogra

    2014-01-01

    Full Text Available Background:peptic ulcers were earlier believed to be caused by dietary factors, gastric acid, and stress. However, in 1983, Warren and Marshall identified the correlation between Helicobacter pylori (H. pylori and peptic ulcers. It is now well established that most of the peptic ulcers occur as a result of H. pylori infection. But the co-relation between perforated peptic ulcer and H. pylori infection is not yet fully established. Aims and objectives : to study the prevalence of H. pylori infection in patients with perforated peptic ulcer. Materials and methods: this was a prospective study carried out in all cases of perforated peptic ulcer reporting in surgical wards of a medical college during 2008-2010. A total of 50 cases, presenting as acute perforation of duodenum and stomach during this period, formed the study group. After resuscitation, all the cases were subjected to emergency exploratory laparotomy. The exact site of perforation was identified, biopsy was taken from the ulcer margin from 2-3 sites and the tissue was sent for H. pylori culture and histopathological examination. Simple closure of perforation, omentoplasty, thorough peritoneal lavage and drainage was carried out. Results: out of the 50 cases of perforated peptic ulcer, 38 happened to be males, and only 12 were females. The age of the patients ranged from 20 to 70 years. All the patients underwent only emergency laparotomy. As many as 46 cases (92% turned out to be positive for H. pylori and only four cases (8% were negative for this infection. Postoperatively, patients who were found to be positive for H. pylori were put on anti-H. pylori treatment. Conclusion: there was a high prevalence of H. pylori infection in patients with perforated gastroduodenal ulcers.

  20. Helicobacter pylori Infection Induces Anemia, Depletes Serum Iron Storage, and Alters Local Iron-Related and Adult Brain Gene Expression in Male INS-GAS Mice.

    Directory of Open Access Journals (Sweden)

    Monika Burns

    Full Text Available Iron deficiency anemia (IDA affects > 500 million people worldwide, and is linked to impaired cognitive development and function in children. Helicobacter pylori, a class 1 carcinogen, infects about half of the world's population, thus creating a high likelihood of overlapping risk. This study determined the effect of H. pylori infection on iron homeostasis in INS-GAS mice. Two replicates of INS-GAS/FVB male mice (n = 9-12/group were dosed with H. pylori (Hp strain SS1 or sham dosed at 6-9 weeks of age, and were necropsied at 27-29 weeks of age. Hematologic and serum iron parameters were evaluated, as was gene expression in gastric and brain tissues. Serum ferritin was lower in Hp SS1-infected mice than uninfected mice (p < 0.0001. Infected mice had a lower red blood cell count (p<0.0001, hematocrit (p < 0.001, and hemoglobin concentration (p <0.0001 than uninfected mice. Relative expression of gastric hepcidin antimicrobial peptide (Hamp was downregulated in mice infected with Hp SS1 compared to sham-dosed controls (p<0.001. Expression of bone morphogenic protein 4 (Bmp4, a growth factor upstream of hepcidin, was downregulated in gastric tissue of Hp SS1-infected mice (p<0.001. Hp SS1-infected mice had downregulated brain expression of tyrosine hydroxylase (Th (p = 0.02. Expression of iron-responsive genes involved in myelination (myelin basic protein (Mbp and proteolipid protein 2 (Plp2 was downregulated in infected mice (p = 0.001 and p = 0.02. Expression of synaptic plasticity markers (brain derived neurotrophic factor 3 (Bdnf3, Psd95 (a membrane associated guanylate kinase, and insulin-like growth factor 1 (Igf1 was also downregulated in Hp SS1-infected mice (p = 0.09, p = 0.04, p = 0.02 respectively. Infection of male INS-GAS mice with Hp SS1, without concurrent dietary iron deficiency, depleted serum ferritin, deregulated gastric and hepatic expression of iron regulatory genes, and altered iron-dependent neural processes. The use of Hp SS

  1. Helicobacter pylori update: gastric cancer, reliable therapy, and possible benefits.

    Science.gov (United States)

    Graham, David Y

    2015-04-01

    Helicobacter pylori infection contributes to the development of diverse gastric and extragastric diseases. The infection is necessary but not sufficient for the development of gastric adenocarcinoma. Its eradication would eliminate a major worldwide cause of cancer death, therefore there is much interest in identifying how, if, and when this can be accomplished. There are several mechanisms by which H pylori contributes to the development of gastric cancer. Gastric adenocarcinoma is one of many cancers associated with inflammation, which is induced by H pylori infection, yet the bacteria also cause genetic and epigenetic changes that lead to genetic instability in gastric epithelial cells. H pylori eradication reduces both. However, many factors must be considered in determining whether treating this bacterial infection will prevent cancer or only reduce its risk-these must be considered in designing reliable and effective eradication therapies. Furthermore, H pylori infection has been proposed to provide some benefits, such as reducing the risks of obesity or childhood asthma. When tested, these hypotheses have not been confirmed and are therefore most likely false. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  2. EGFR tyrosine kinase inhibitory peptide attenuates Helicobacter pylori-mediated hyper-proliferation in AGS enteric epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Himaya, S.W.A. [Marine Bio-Process Research Center, Pukyong National University, Nam-Gu, Busan, 608-737 (Korea, Republic of); Dewapriya, Pradeep [Department of Chemistry, Pukyong National University, Nam-Gu, Busan, 608-737 (Korea, Republic of); Kim, Se-Kwon, E-mail: sknkim@pknu.ac.kr [Marine Bio-Process Research Center, Pukyong National University, Nam-Gu, Busan, 608-737 (Korea, Republic of); Department of Chemistry, Pukyong National University, Nam-Gu, Busan, 608-737 (Korea, Republic of)

    2013-06-15

    Helicobacter pylori infection is one of the most critical causes of stomach cancer. The current study was conducted to explore the protective effects of an isolated active peptide H-P-6 (Pro-Gln-Pro-Lys-Val-Leu-Asp-Ser) from microbial hydrolysates of Chlamydomonas sp. against H. pylori-induced carcinogenesis. The peptide H-P-6 has effectively suppressed H. pylori-induced hyper-proliferation and migration of gastric epithelial cells (AGS). However, the peptide did not inhibit the viability of the bacteria or invasion into AGS cells. Therefore, the effect of the peptide on regulating H. pylori-induced molecular signaling was investigated. The results indicated that H. pylori activates the EGFR tyrosine kinase signaling and nuclear translocation of the β-catenin. The EGFR activation has led to the up-regulation of PI3K/Akt signaling pathway. Moreover, the nuclear translocation levels of β-catenin were significantly increased as a result of Akt mediated down-regulation of GSK3/β protein levels in the cytoplasm. Both of these consequences have resulted in increased expression of cell survival and migration related genes such as c-Myc, cyclin-D, MMP-2 and matrilysin. Interestingly, the isolated peptide potently inhibited H. pylori-mediated EGFR activation and thereby down-regulated the subsequent P13K/Akt signaling leading to β-catenin nuclear translocation. The effect of the peptide was confirmed with the use of EGFR tyrosine kinase inhibitor AG1487 and molecular docking studies. Collectively this study identifies a potent peptide which regulates the H. pylori-induced hyper-proliferation and migration of AGS cells at molecular level. - Highlights: • Chlamydomonas sp. derived peptide H-P-6 inhibits H. pylori-induced pathogenesis. • H-P-6 suppresses H. pylori-induced hyper-proliferation and migration of AGS cells. • The peptide inhibits H. pylori-induced EGFR activation.

  3. Inflammation, Immunity, and Vaccines for Helicobacter pylori Infection

    DEFF Research Database (Denmark)

    Walduck, Anna; Andersen, Leif P; Raghavan, Sukanya

    2015-01-01

    studies that contribute with new insights in the host response to H. pylori infection. Also, the adaptive immune response to H. pylori and particularly the role of IL-22 have been addressed in some studies. These advances may improve vaccine development where new strategies have been published. Two major...... studies analyzed H. pylori genomes of 39 worldwide strains and looked at the protein profiles. In addition, multi-epitope vaccines for therapeutic use have been investigated. Studies on different adjuvants and delivery systems have also given us new insights. This review presents articles from the last...... year that reveal detailed insight into immunity and regulation of inflammation, the contribution of immune cells to the development of gastric cancer, and understanding mechanisms of vaccine-induced protection....

  4. Oxidative DNA damage and oxidized low density lipoprotein in Type II diabetes mellitus among patients with Helicobacter pylori infection.

    Science.gov (United States)

    Nasif, Wesam Ahmed; Mukhtar, Mohammed Hasan; Nour Eldein, Mohammed Mahmoud; Ashgar, Sami Sadagah

    2016-01-01

    Helicobacter pylori (H. pylori) infection is reported to be associated with various extragastrointestinal conditions such as insulin resistance, diabetes mellitus and metabolic syndrome. H. pylori infection and type 2 diabetes mellitus (T2DM) are associated with oxidative stress, this cross-relation between H. pylori induced infection in T2DM and oxidative damage is still debated. Thus, the question arises whether an increase in the serum level of 8-OHdG and Ox-LDL will occurs in patients with T2DM infected H. pylori; this will be through determination and compare frequency of H. pylori infection in T2DM and non-diabetic patients. 100 patients presented with history of epigastric discomfort for more than 1 month; 50 patients with T2DM and 50 non-diabetics. Anti-H. pylori IgG using ELISA, fasting and postprandial glucose level, glycated hemoglobin (HbA1c) and body mass index (BMI) was calculated. Serum 8-OHdG and Ox-LDL was measured using ELISA for the 100 patients and 50 control subject. Rates of H. pylori infection of T2DM and non-diabetic were 66 and 58 %, respectively, (p = 0.001). H. pylori IgG antibody was not correlated with HbA1c either in T2DM (p = 0.06) or non-diabetic (p = 0.25). Serum 8-OHdG level in T2DM with positive H. pylori infection showed a significant difference compared to non-diabetics with positive H. pylori infection (p = 0.001) and higher than that in T2DM with negative H. pylori. A correlation between 8-OHdG concentration and HbA1c in T2DM patients infected with H. pylori was observed (r = 0.39, p = 0.02). Serum Ox-LDL level in T2DM with positive H. pylori infection showed a significant difference compared to diabetics with both negative H. pylori infection and in non-diabetics with positive H. pylori infection (p = 0.001). Increased levels of oxidative DNA damage (8-OHdG) and Ox-LDL suggest the mechanistic link between H. pylori infection combined with diabetes and increased generation of ROS and could play as an important

  5. Down-Regulation of miR-141 Induced by Helicobacter Pylori Promotes the Invasion of Gastric Cancer by Targeting STAT4

    Directory of Open Access Journals (Sweden)

    Xiaoying Zhou

    2014-04-01

    Full Text Available Background: The association between Helicobacter pylori infection and gastric cancer has been identified recently. However, the molecular mechanism remained largely unknown. Methods and Results: We found that miR-141 was decreased in Helicobacter pylori positive specimens (n=75 compared with negative tissues (n=75. The knockdown of miR-141 enhanced the invasion ability of gastric cancer cells; meanwhile, over-expression of miR-141 could inhibit the abilities of gastric cancer cells in vitro. A luciferase assay revealed that miR-141 was directly bound to the 3'-untranslated regions (3'-UTR of STAT4. STAT4 was found up-regulated at mRNA and protein levels, as shown by qRT-PCR and western blot. Over-expression of STAT4 was used to mimic miR-141 action in the invasion of gastric cancer. Conclusion: MiR-141 may play a pivotal role in controlling gastric cancer invasion through regulating STAT4 and maybe a potential target to treat gastric cancer.

  6. H pylori infection causes chronic pancreatitis in Mongolian gerbils

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate whether chronic H pylori infection has the potential to induce pancreatitis in the Mongolian gerbil model, and whether it is dependent on an intact type Ⅳ secretion system.METHODS: Mongolian gerbils were infected with wild type (WT) H pyloritype Ⅰ strain B128 or its isogenic mutant B128 Acag Y (defective type Ⅳ secretion). After seven months of infection, H pylori was reisolated from antrum and corpus and H pylori DNA was analyzed by seminested polymerase chain reaction (PCR). Inflammation and histological changes were documented in the gastric antrum, corpus, and pancreas by immunohistochemistry.Cytokine mRNA, gastric pH, plasma gastrin, amylase,lipase, and glucose levels were determined.RESULTS: The H pylori infection rate was 95%.Eight infected animals, but none of the uninfected group, developed transmural inflammation and chronic pancreatitis. Extensive interstitial fibrosis and inflammation of the pancreatic lobe adjacent to the antrum was confirmed by trichrome stain, and immunohistochemically. Pro-inflammatory cytokine mRNA was significantly increased in the antral mucosa of all infected gerbils. In the corpus, only cytokine levels of WT-infected animals and those developing transmural inflammation and pancreatitis were significantly increased.Levels of lipase, but not glucose or amylase levels, were significantly reduced in the pancreatitis group. H pylori DNA was detected in infected antral and corpus tissue,but not in the pancreas.CONCLUSION: H pylori infection is able to induce chronic pancreatitis in Mongolian gerbils independently of the type Ⅳ secretion system, probably by an indirect mechanism associated with a penetrating ulcer.

  7. Anti-bacterial effects of enzymatically-isolated sialic acid from glycomacropeptide in a Helicobacter pylori-infected murine model

    Science.gov (United States)

    Noh, Hye-Ji; Koh, Hong Bum; Kim, Hee-Kyoung; Cho, Hyang Hyun

    2017-01-01

    BACKGROUND/OBJECTIVES Helicobacter pylori (H. pylori) colonization of the stomach mucosa and duodenum is the major cause of acute and chronic gastroduodenal pathology in humans. Efforts to find effective anti-bacterial strategies against H. pylori for the non-antibiotic control of H. pylori infection are urgently required. In this study, we used whey to prepare glycomacropeptide (GMP), from which sialic acid (G-SA) was enzymatically isolated. We investigated the anti-bacterial effects of G-SA against H. pylori in vitro and in an H. pylori-infected murine model. MATERIALS/METHODS The anti-bacterial activity of G-SA was measured in vitro using the macrodilution method, and interleukin-8 (IL-8) production was measured in H. pylori and AGS cell co-cultures by ELISA. For in vivo study, G-SA 5 g/kg body weight (bw)/day and H. pylori were administered to mice three times over one week. After one week, G-SA 5 g/kg bw/day alone was administered every day for one week. Tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and IL-10 levels were measured by ELISA to determine the anti-inflammatory effects of G-SA. In addition, real-time PCR was performed to measure the genetic expression of cytotoxin-associated gene A (cagA). RESULTS G-SA inhibited the growth of H. pylori and suppressed IL-8 production in H. pylori and in AGS cell co-cultures in vitro. In the in vivo assay, administration of G-SA reduced levels of IL-1β and IL-6 pro-inflammatory cytokines whereas IL-10 level increased. Also, G-SA suppressed the expression of cagA in the stomach of H. pylori-infected mice. CONCLUSION G-SA possesses anti-H. pylori activity as well as an anti-H. pylori-induced gastric inflammatory effect in an experimental H. pylori-infected murine model. G-SA has potential as an alternative to antibiotics for the prevention of H. pylori infection and H. pylori-induced gastric disease prevention. PMID:28194260

  8. Brain-gut axis in the pathogenesis of Helicobacter pylori infection

    Science.gov (United States)

    Budzyński, Jacek; Kłopocka, Maria

    2014-01-01

    Helicobacter pylori (H. pylori) infection is the main pathogenic factor for upper digestive tract organic diseases. In addition to direct cytotoxic and proinflammatory effects, H. pylori infection may also induce abnormalities indirectly by affecting the brain-gut axis, similar to other microorganisms present in the alimentary tract. The brain-gut axis integrates the central, peripheral, enteric and autonomic nervous systems, as well as the endocrine and immunological systems, with gastrointestinal functions and environmental stimuli, including gastric and intestinal microbiota. The bidirectional relationship between H. pylori infection and the brain-gut axis influences both the contagion process and the host’s neuroendocrine-immunological reaction to it, resulting in alterations in cognitive functions, food intake and appetite, immunological response, and modification of symptom sensitivity thresholds. Furthermore, disturbances in the upper and lower digestive tract permeability, motility and secretion can occur, mainly as a form of irritable bowel syndrome. Many of these abnormalities disappear following H. pylori eradication. H. pylori may have direct neurotoxic effects that lead to alteration of the brain-gut axis through the activation of neurogenic inflammatory processes, or by microelement deficiency secondary to functional and morphological changes in the digestive tract. In digestive tissue, H. pylori can alter signaling in the brain-gut axis by mast cells, the main brain-gut axis effector, as H. pylori infection is associated with decreased mast cell infiltration in the digestive tract. Nevertheless, unequivocal data concerning the direct and immediate effect of H. pylori infection on the brain-gut axis are still lacking. Therefore, further studies evaluating the clinical importance of these host-bacteria interactions will improve our understanding of H. pylori infection pathophysiology and suggest new therapeutic approaches. PMID:24833851

  9. Anti-Helicobacter pylori activity and immunostimulatory effect of extracts from Byrsonima crassa Nied. (Malpighiaceae

    Directory of Open Access Journals (Sweden)

    Vilegas Wagner

    2009-01-01

    Full Text Available Abstract Background Several in vitro studies have looked at the effect of medicinal plant extracts against Helicobacter pylori (H. pylori. Regardless of the popular use of Byrsonima crassa (B. crassa as antiemetic, diuretic, febrifuge, to treat diarrhea, gastritis and ulcers, there is no data on its effects against H. pylori. In this study, we evaluated the anti-H. pylori of B. crassa leaves extracts and its effects on reactive oxygen/nitrogen intermediates induction by murine peritoneal macrophages. Methods The minimal inhibitory concentration (MIC was determined by broth microdilution method and the production of hydrogen peroxide (H2O2 and nitric oxide (NO by the horseradish peroxidase-dependent oxidation of phenol red and Griess reaction, respectively. Results The methanolic (MeOH and chloroformic (CHCl3 extracts inhibit, in vitro, the growth of H. pylori with MIC value of 1024 μg/ml. The MeOH extract induced the production H2O2 and NO, but CHCl3 extract only NO. Conclusion Based in our results, B. crassa can be considered a source of compounds with anti-H. pylori activity, but its use should be done with caution in treatment of the gastritis and peptic ulcers, since the reactive oxygen/nitrogen intermediates are involved in the pathogenesis of gastric mucosal injury induced by ulcerogenic agents and H. pylori infections.

  10. Helicobacter pylori in lacrimal secretions.

    Science.gov (United States)

    Batioglu-Karaaltin, Aysegul; Saatci, Ozlem; Akpinar, Meltem; Celik, Melih Ozgür; Develioglu, Omer; Yigit, Ozgur; Külekçi, Mehmet; Akarsubaşı, Alper Tunga

    2016-03-01

    The aim of this study was to investigate the presence of Helicobacter pylori in human lacrimal and nasal secretions. Eighty patients with complaints of dyspepsia who had undergone endoscopies and gastric antrum biopsies were included in the study. A total of five specimens, including 2 lacrimal secretion samples, 2 nasal mucosal swab samples, and 1 gastric antrum biopsy, were collected from each patient and investigated with polymerase chain reaction (PCR) methods consisting of the urease enzyme coding gene GlmM (UreC) and the H pylori-specific 16S rRNA coding gene. The Reflux Symptom Index and ophthalmologic complaints of the patients were recorded. The detected positivity rates of the H pylori 16S rRNA coding gene in gastric biopsies and nasal mucous and lacrimal secretions were 55, 11.2, and 20%, respectively. The patients were grouped as gastric-antrum-biopsy-negative (Group I [n = 36]) and -positive (Group II [n = 44). In Group II, H pylori positivity in the lacrimal and nasal mucous secretions was 36.3 and 18%, respectively. A comparison between the groups in terms of H pylori presence in nasal mucous and lacrimal secretions yielded statistically significant differences (p = 0.0001, p = 0.003). The simultaneous presence of H pylori in nasal mucous and lacrimal secretions was 13.6% in Group II. H pylori positivity in nasal mucous and lacrimal secretions had a positive moderate correlation (r = 0.40; p = 0.0003). The present study is the first report on the presence of H pylori in lacrimal secretions through nested PCR, which suggested the presence of a number of mechanisms for H pylori transmission to lacrimal secretions.

  11. Effect of pretreatment with Ethanol or Ammonium Hydroxide on Helicobacter Pylori colonization in the stomach of rats

    Directory of Open Access Journals (Sweden)

    Fahimi F

    2002-05-01

    Full Text Available Animal models for H.pylori infection have been developed to clarify the pathogenesis, testing new therapies and developing vaccines against human H.pylori infection. Although rats have been used extensively for gastric ulceration and acid secretion studies, the animal is not normally infected with H.pylori.Several chemicals such as ethanol and ammonium hydroxide can induce gastric erosion and interact with gastric mucosal defense mechanisms. The aim of the present study was to investigate the effects of pretreatment with the gastroinvasive agents on colonization of H. pylori with the gastroinvasive agents on colonization of H. pylori in not germ-free rats in order to overcome the resistance against H. pylori in rats. After 24 h fasting, the rats were divided into three major groups. Animals in the first group were not pretreated with any chemicals. The two other groups were pretreated with ethanol (60% or ammonium hydroxide (1% before inoculation of 1 mL H. pylori suspension (3×108 cfu/ml. The results showed that H. pylori could not colonize in rats, even with ethanol or ammonium hydroxide pretreatment. An understanding of the mechanism of this resistance can help researchers to develop new therapeutic or preventive drugs against H. pylori and it is recommended to perform more investigation to clarify the reason of this resistance

  12. The Helicobacter pylori L-form: formation and isolation in the human bile cultures in vitro and in the gallbladders of patients with biliary diseases.

    Science.gov (United States)

    Wang, Dan N; Ding, Wen J; Pan, Yao Z; Tang, Ke L; Wang, Tao; She, Xiao L; Wang, He

    2015-04-01

    The Helicobacter pylori is considered the important causative agent causing biliary diseases, but the H. pylori can be isolated from very few gallbladder specimens with diseases. We studied the formation of H. pylori L-forms in bile in vitro and isolated the H. pylori L-forms from gallbladder of patients with biliary diseases. We inoculated the H. pylori into the human bile to induce the L-form in vitro. The gallbladder specimens were collected from patients with biliary diseases to isolate the bacterial L-forms by the nonhigh osmotic isolation technique, and the H. pylori L-forms in the L-form isolates were identified by the gene assay for the H. pylori-specific genes 16S rRNA and UreA. The H. Pylori cannot be isolated from the bile-induced cultures, but the H. pylori L-form can be isolated from the H. pylori-negative bile-induced cultures. The L-form isolates of bile-induced cultures showed a positive reaction of the H. pylori-specific genes by PCR, and the coincidence ratio of the nucleotide sequences between the L-forms and the H. pylori is 99%. The isolation rate of bacteria L-form is 93.2% in the gallbladder specimens with bacteria-negative isolation culture by the nonhigh osmotic isolation technique, and the positive rate of the H. pylori-specific genes in the L-form isolates is 7.1% in the bacterial L-form-positive isolation cultures by the PCR. H. pylori can be rapidly induced into the L-form in the human bile; the L-form, as the latent bacteria, can live in the host gallbladder for a long times, and they made the host became a latent carrier of the H. pylori L-form. The H. pylori L-form can be isolated by the nonhigh osmotic isolation technique, and the variant can be identified by the gene assay for the H. pylori-specific genes 16S rRNA and reA. © 2014 John Wiley & Sons Ltd.

  13. Helicobacter pylori neutrophil-activating protein induces release of histamine and interleukin-6 through G protein-mediated MAPKs and PI3K/Akt pathways in HMC-1 cells.

    Science.gov (United States)

    Tsai, Chung-Che; Kuo, Ting-Yu; Hong, Zhi-Wei; Yeh, Ying-Chieh; Shih, Kuo-Shun; Du, Shin-Yi; Fu, Hua-Wen

    2015-01-01

    Helicobacter pylori neutrophil-activating protein (HP-NAP) activates several innate leukocytes including neutrophils, monocytes, and mast cells. It has been reported that HP-NAP induces degranulation and interleukin-6 (IL-6) secretion of rat peritoneal mast cells. However, the molecular mechanism is not very clear. Here, we show that HP-NAP activates human mast cell line-1 (HMC-1) cells to secrete histamine and IL-6. The secretion depends on pertussis toxin (PTX)-sensitive heterotrimeric G proteins but not on Toll-like receptor 2. Moreover, HP-NAP induces PTX-sensitive G protein-mediated activation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38-mitogen-activated protein kinase (p38 MAPK), and Akt in HMC-1 cells. Inhibition of ERK1/2, p38 MAPK, or phosphatidylinositol 3-kinase (PI3K) suppresses HP-NAP-induced release of histamine and IL-6 from HMC-1 cells. Thus, the activation of HMC-1 cells by HP-NAP is through Gi-linked G protein-coupled receptor-mediated MAPKs and PI3K/Akt pathways.

  14. Helicobacter pylori infection inhibits phagocyte clearance of apoptotic gastric epithelial cells.

    Science.gov (United States)

    Bimczok, Diane; Smythies, Lesley E; Waites, Ken B; Grams, Jayleen M; Stahl, Richard D; Mannon, Peter J; Peter, Shajan; Wilcox, C Mel; Harris, Paul R; Das, Soumita; Ernst, Peter B; Smith, Phillip D

    2013-06-15

    Increased apoptotic death of gastric epithelial cells is a hallmark of Helicobacter pylori infection, and altered epithelial cell turnover is an important contributor to gastric carcinogenesis. To address the fate of apoptotic gastric epithelial cells and their role in H. pylori mucosal disease, we investigated phagocyte clearance of apoptotic gastric epithelial cells in H. pylori infection. Human gastric mononuclear phagocytes were analyzed for their ability to take up apoptotic epithelial cells (AECs) in vivo using immunofluorescence analysis. We then used primary human gastric epithelial cells induced to undergo apoptosis by exposure to live H. pylori to study apoptotic cell uptake by autologous monocyte-derived macrophages. We show that HLA-DR(+) mononuclear phagocytes in human gastric mucosa contain cytokeratin-positive and TUNEL-positive AEC material, indicating that gastric phagocytes are involved in AEC clearance. We further show that H. pylori both increased apoptosis in primary gastric epithelial cells and decreased phagocytosis of the AECs by autologous monocyte-derived macrophages. Reduced macrophage clearance of apoptotic cells was mediated in part by H. pylori-induced macrophage TNF-α, which was expressed at higher levels in H. pylori-infected, compared with uninfected, gastric mucosa. Importantly, we show that H. pylori-infected gastric mucosa contained significantly higher numbers of AECs and higher levels of nonphagocytosed TUNEL-positive apoptotic material, consistent with a defect in apoptotic cell clearance. Thus, as shown in other autoimmune and chronic inflammatory diseases, insufficient phagocyte clearance may contribute to the chronic and self-perpetuating inflammation in human H. pylori infection.

  15. [Helicobacter pylori -- 2014].

    Science.gov (United States)

    Buzás, György Miklós

    2015-02-08

    The author reviews the main achievements in Helicobacter pylori research in the past 2 years. Of the more than 1000 microRNAs described thus far, sets of over- and underexpressed samples were identified that are associated with either gastric cancer or precancerous lesions, and some of them could be either markers or therapeutic targets in the near future. Meta-analyses involved 95 new publications: the association between infection and oesophageal, colorectal, pancreatic and liver carcinomas is supported by the increased odds ratios, but the results do not reach the strength seen in gastric carcinoma. Epstein-Barr virus is an emerging pathogen: 10% of gastric cancers are virus-associated; the prevalence of the virus in normal mucosa, chronic gastritis and peptic ulcer are currently being studied. Current Helicobacter pylori eradication regimens frequently achieve suboptimal results: a few optimisation methods are presented, although not all are supported by the meta-analyses. In 2013, the European Helicobacter Study Group proposed the development of a pan-European registry; data from 5792 patients registered so far indicated that many therapeutic regimens resulted in a low eradication rate. In 2013, the Healthy Stomach Initiative was started with the aim of supporting and disseminating research performed in the field of healthy and diseased stomachs.

  16. Helicobacter pylori infection in pediatrics

    DEFF Research Database (Denmark)

    Wewer, Anne Vibeke; Kalach, Nicolas

    2003-01-01

    A high prevalence and early colonization of Helicobacter pylori infection in childhood was described again this year in developing countries in contrast to developed ones. Upper gastrointestinal endoscopy including gastric biopsies remains the diagnostic gold standard method for this infection...

  17. Management of Helicobacter pylori infections

    NARCIS (Netherlands)

    Abadi, Amin Talebi Bezmin; Kusters, Johannes G

    2016-01-01

    BACKGROUND: Infection with Helicobacter pylori is associated with severe digestive diseases including chronic gastritis, peptic ulcer disease, and gastric cancer. Successful eradication of this common gastric pathogen in individual patients is known to prevent the occurrence of peptic ulcer disease

  18. Management of Helicobacter pylori infections

    NARCIS (Netherlands)

    Abadi, Amin Talebi Bezmin; Kusters, Johannes G

    2016-01-01

    BACKGROUND: Infection with Helicobacter pylori is associated with severe digestive diseases including chronic gastritis, peptic ulcer disease, and gastric cancer. Successful eradication of this common gastric pathogen in individual patients is known to prevent the occurrence of peptic ulcer disease

  19. Gastric Carcinogenesis and Underlying Molecular Mechanisms: Helicobacter pylori and Novel Targeted Therapy

    Directory of Open Access Journals (Sweden)

    Toshihiro Nishizawa

    2015-01-01

    Full Text Available The oxygen-derived free radicals that are released from activated neutrophils are one of the cytotoxic factors of Helicobacter pylori-induced gastric mucosal injury. Increased cytidine deaminase activity in H. pylori-infected gastric tissues promotes the accumulation of various mutations and might promote gastric carcinogenesis. Cytotoxin-associated gene A (CagA is delivered into gastric epithelial cells via bacterial type IV secretion system, and it causes inflammation and activation of oncogenic pathways. H. pylori infection induces epigenetic transformations, such as aberrant promoter methylation in tumor-suppressor genes. Aberrant expression of microRNAs is also reportedly linked to gastric tumorogenesis. Moreover, recent advances in molecular targeting therapies provided a new interesting weapon to treat advanced gastric cancer through anti-human epidermal growth factor receptor 2 (HER-2 therapies. This updated review article highlights possible mechanisms of gastric carcinogenesis including H. pylori-associated factors.

  20. Regulation of Helicobacter pylori Virulence Within the Context of Iron Deficiency.

    Science.gov (United States)

    Noto, Jennifer M; Lee, Josephine Y; Gaddy, Jennifer A; Cover, Timothy L; Amieva, Manuel R; Peek, Richard M

    2015-06-01

    Helicobacter pylori strains that harbor the oncoprotein CagA increase gastric cancer risk, and this risk is augmented under iron-deficient conditions. We demonstrate here that iron depletion induces coccoid morphology in strains lacking cagA. To evaluate the stability of augmented H. pylori virulence phenotypes stimulated by low-iron conditions, H. pylori isolated from iron-depleted conditions in vivo were serially passaged in vitro. Long-term passage decreased the ability of hypervirulent strains to translocate CagA or induce interleukin 8, indicating that hypervirulent phenotypes stimulated by low-level iron conditions are reversible. Therefore, rectifying iron deficiency may attenuate disease among H. pylori-infected persons with no response to antibiotics.

  1. Comparison of three diagnostic methods to confirm Helicobacter pylori infection

    Directory of Open Access Journals (Sweden)

    Opavski Nataša

    2007-01-01

    Full Text Available Introduction: Helicobacter pylori induces gastric inflammation in host and such gastritis increases the risk of gastric and duodenal ulceration as well as adenocarcinoma. Because peptic ulcer disease is the major cause of morbidity, accurate diagnosis of H. pylori infection is very important. Unfortunately, there is no gold standard among diagnostic tests for Helicobacter infections. If gastroscopy is performed, histopathology and urease test are the most often used. Still, culturing of this bacterium is essential for drug susceptibility testing and analysis of virulence factors. Objective The aim of this study was to compare three diagnostic procedures - histopathology, urease test and culture, which are used to verify H. pylori infection. Method Three pairs of gastric mucosal biopsy specimens were collected from each of 28 dyspeptic patients undergoing endoscopy. Nineteen patients were not pretreated with antibiotics, while nine had received eradication therapy earlier. One pair of biopsy specimens was used for histopathologic examination, the second for urease test and the third was simultaneously cultured on nonselective and selective solid media. Isolate was identified as H. pylori on the basis of colony morphology, morphological properties and biochemical tests. Results In 14 out of 28 patients, H. pylori infection was confirmed on the basis of results of all diagnostic procedures. The concordance of these three methods was very good, because the results of histopathology, urease test and culture corresponded in 26 from 28 patients. Conclusion The conclusion of our study is that culture, as the method with high degree of concordance with other two procedures and the only that can give information on drug susceptibility of Helicobacter, is recommended for diagnosis of Helicobacter pylori infection along with histopathology and urease test.

  2. Metabolic consequences of Helicobacter pylori infection and eradication.

    Science.gov (United States)

    Buzás, György Miklós

    2014-05-14

    Helicobacter pylori (H. pylori) is still the most prevalent infection of the world. Colonization of the stomach by this agent will invariably induce chronic gastritis which is a low-grade inflammatory state leading to local complications (peptic ulcer, gastric cancer, lymphoma) and remote manifestations. While H. pylori does not enter circulation, these extragastric manifestations are probably mediated by the cytokines and acute phase proteins produced by the inflammed mucosa. The epidemiologic link between the H. pylori infection and metabolic changes is inconstant and controversial. Growth delay was described mainly in low-income regions with high prevalence of the infection, where probably other nutritional and social factors contribute to it. The timely eradication of the infection will lead to a more healthy development of the young population, along with preventing peptic ulcers and gastric cancer An increase of total, low density lipoprotein and high density liporotein cholesterol levels in some infected people creates an atherogenic lipid profile which could promote atherosclerosis with its complications, myocardial infarction, stroke and peripheral vascular disease. Well designed and adequately powered long-term studies are required to see whether eradication of the infection will prevent these conditions. In case of glucose metabolism, the most consistent association was found between H. pylori and insulin resistance: again, proof that eradication prevents this common metabolic disturbance is expected. The results of eradication with standard regimens in diabetics are significantly worse than in non-diabetic patients, thus, more active regimens must be found to obtain better results. Successful eradication itself led to an increase of body mass index and cholesterol levels in some populations, while in others no such changes were encountered. Uncertainities of the metabolic consequences of H. pylori infection must be clarified in the future.

  3. Pathogenesis of Helicobacter pylori infection.

    Science.gov (United States)

    Hofman, Paul; Waidner, Barbara; Hofman, Véronique; Bereswill, Stefan; Brest, Patrick; Kist, Manfred

    2004-01-01

    Research in the last year has provided new insights into the function of the the cag-associated type IV secretion system and the vacuolating toxin VacA. A quite new aspect was disclosed by the finding that Helicobacter pylori in Mongolian gerbils colonizes a very distinct topology in the gastric mucous layer, obviously providing optimal conditions for long-term survival. Further research activities focused on H. pylori ammonia and metal metabolism as well as on bacterial stress defence mechanisms. Differential expression of approximately 7% of the bacterial genome was found at low pH suggesting that H. pylori has evolved a multitude of acid-adaptive mechanisms. VacA was shown to interrupt phagosome maturation in macrophage cell lines as well as to modulate and interfere with T lymphocyte immunological functions. Gastric mucosa as well as the H. pylori-infected epithelial cell line AGS strongly express IL-8 receptor A and B, which might contribute to the augmentation of the inflammatory response. Accumulating evidence implicates genetic variation in the inflammatory response to H. pylori in the etiology of the increased risk of gastric cancer after H. pylori infection. The chronic imbalance between apoptosis and cell proliferation is the first step of gastric carcinogenesis. In this regard, it was demonstrated that coexpression of two H. pylori proteins, CagA and HspB, in AGS cells, caused an increase in E2F transcription factor, cyclin D3, and phosphorylated retinoblastoma protein. Taken together, we now have a better understanding of the role of different virulence factors of H. pylori. There is still a lot to be learned, but the promising discoveries summarized here, demonstrate that the investigation of the bacterial survival strategies will give novel insights into pathogenesis and disease development.

  4. Genipin-cross-linked fucose-chitosan/heparin nanoparticles for the eradication of Helicobacter pylori.

    Science.gov (United States)

    Lin, Yu-Hsin; Tsai, Shih-Chang; Lai, Chih-Ho; Lee, Che-Hsin; He, Zih Sian; Tseng, Guan-Chin

    2013-06-01

    Helicobacter pylori is a significant human pathogen that recognizes specific carbohydrate receptors, such as the fucose receptor, and produces the vacuolating cytotoxin, which induces inflammatory responses and modulates the cell-cell junction integrity of the gastric epithelium. The clinical applicability of topical antimicrobial agents was needed to complete the eradication of H. pylori in the infected fundal area. In the present study, we combined fucose-conjugated chitosan and genipin-cross-linking technologies in preparing multifunctional genipin-cross-linked fucose-chitosan/heparin nanoparticles to encapsulate amoxicillin of targeting and directly make contact with the region of microorganism on the gastric epithelium. The results show that the nanoparticles effectively reduced drug release at gastric acids and then released amoxicillin in an H. pylori survival situation to inhibit H. pylori growth and reduce disruption of the cell-cell junction protein in areas of H. pylori infection. Furthermore, with amoxicillin-loaded nanoparticles, a more complete H. pylori clearance effect was observed, and H. pylori-associated gastric inflammation in an infected animal model was effectively reduced.

  5. Helicobacter pylori Genotypes Associated with Gastric Histo-Pathological Damages in a Moroccan Population

    Science.gov (United States)

    Alaoui Boukhris, Samia; Amarti, Afaf; El Rhazi, Karima; El Khadir, Mounia; Benajah, Dafr-Allah; Ibrahimi, Sidi Adil; Nejjari, Chakib; Mahmoud, Mustapha; Souleimani, Abdellah; Bennani, Bahia

    2013-01-01

    H. pylori persistent infection induces chronic gastritis and is associated with peptic ulcer disease and gastric carcinoma development. The severity of these diseases is related to human’s genetic diversity, H. pylori genetic variability and environmental factors. To identify the prevalence of histo-pathological damages caused by H. pylori infection in Moroccan population, and to determine their association to H. pylori genotypes, a prospective study has been conducted during 3 years on patients attending the gastroenterology department of Hassan II University Hospital (CHU) of Fez, Morocco. A total of 801 Moroccan adults’ patients were recruited; H. pylori was diagnosed and genotyped by PCR in biopsy specimens and histological exam was performed. We found a high rate of glandular atrophy. Chronic inflammation, neutrophil activity and glandular atrophy showed statistically significant association with H. pylori infection. However, intestinal metaplasia was inversely associated to this infection and no association was observed with gastric cancer cases. A statistically significant association was found between intestinal metaplasia and vacAs1 and vac Am1 genotypes in patients aged 50 years and more but not in younger. This last genotype is also associated to gastric cancer. In this study, gastric cancer showed no significant association with H. pylori. Further studies are warranted to determine the role of other etiological agents such as Epstein-Barr virus, human papillomavirus and possibly environmental and dietetic factors in the occurrence of this pathology. PMID:24349327

  6. Molecular detection and corelation of Helicobacter pylori in dental plaque and gastric biopsies of dyspeptic patients

    Science.gov (United States)

    Bharath, T Sreenivasa; Reddy, M Sesha; Dhanapal, Raghu; Raj Kumar, N Govind; Neeladri Raju, PV; Saraswathi, TR

    2014-01-01

    Helicobacter pylori is a microaerophilic organism, which colonizes in the gastric mucosa. Its role in etiology and development of acute and chronic gastritis and peptic ulcer diseases is scientifically proved. Oral cavity especially supragingival, subgingival plaque and so forth simulate the same microaerophilic environment favorable for the growth of this bacterium. Aim: Detection of H. pylori simultaneously in the oral cavity and gastric mucosa of patients suffering from gastric pathologies. Objectives: To detect H. pylori in the oral cavity and gastric mucosa using endoscopy, urease test and real-time polymerase chain reaction (PCR) (urease A gene). Determining its association and corelation with patient demographics, oral hygiene maintenance and periodontal disease status. Materials and Methods: Endoscopic examination, oral findings oral hygiene index-simplified (OHI-S) and community periodontal index and treatment needs (CPITN) indices were recorded. Antral biopsies and supragingival plaque samples were taken from 56 dyspeptic adult patients. The collected samples were subjected to histological examination, urease broth test and urease A gene amplification using real-time PCR. Result: H. pylori was detected in the supragingival plaque of individuals with H. pylori-induced gastric diseases using rapid urease test and real-time PCR analysis. Occurrence of same strain of H. pylori simultaneously in plaque and gastric mucosa was observed. Positive correlation was obtained between the collected indices and quantity of H. pylori colonization. PMID:24959032

  7. Role of Regulatory T-cells in Different Clinical Expressions of Helicobacter pylori Infection.

    Science.gov (United States)

    Bagheri, Nader; Azadegan-Dehkordi, Fatemeh; Rahimian, Ghorbanali; Rafieian-Kopaei, Mahmoud; Shirzad, Hedayatollah

    2016-05-01

    Helicobacter pylori (H. pylori) colonization induces vigorous innate and specific immune responses; however, the infection does not disappear and a chronic active gastritis continues if left untreated. It has been shown that the topographical pattern and immune response of gastritis are the main reasons for the bacteria persistence and the clinical outcome. Gastritis due to H. pylori is caused by a complicated interaction among a variety of T cell subsets. Regulatory T (Treg) cells suppressing the immune response of antigen-specific T-cells have recently been demonstrated to play a key role in chronic inflammation by immunologic tolerance. Treg cells have been identified as the major regulatory component of the adaptive immune response and being involved in H. pylori-related inflammation and bacterial persistence. There have been many controversies over the role of Treg cells in H. pylori infection. Many studies have shown that the local Treg response protects the gastric mucosa from intensified inflammation and tissue damage, and the risk of H. pylori-associated diseases has an inverse correlation with Treg accumulation, even if the decrease in the inflammatory response is recognized by Treg it causes increase in bacterial density. This paper reviews the role of Treg in different clinical expressions of H. pylori infection.

  8. Molecular detection and corelation of Helicobacter pylori in dental plaque and gastric biopsies of dyspeptic patients

    Directory of Open Access Journals (Sweden)

    T Sreenivasa Bharath

    2014-01-01

    Full Text Available Helicobacter pylori is a microaerophilic organism, which colonizes in the gastric mucosa. Its role in etiology and development of acute and chronic gastritis and peptic ulcer diseases is scientifically proved. Oral cavity especially supragingival, subgingival plaque and so forth simulate the same microaerophilic environment favorable for the growth of this bacterium. Aim: Detection of H. pylori simultaneously in the oral cavity and gastric mucosa of patients suffering from gastric pathologies. Objectives: To detect H. pylori in the oral cavity and gastric mucosa using endoscopy, urease test and real-time polymerase chain reaction (PCR (urease A gene. Determining its association and corelation with patient demographics, oral hygiene maintenance and periodontal disease status. Materials and Methods: Endoscopic examination, oral findings oral hygiene index-simplified (OHI-S and community periodontal index and treatment needs (CPITN indices were recorded. Antral biopsies and supragingival plaque samples were taken from 56 dyspeptic adult patients. The collected samples were subjected to histological examination, urease broth test and urease A gene amplification using real-time PCR. Result: H. pylori was detected in the supragingival plaque of individuals with H. pylori-induced gastric diseases using rapid urease test and real-time PCR analysis. Occurrence of same strain of H. pylori simultaneously in plaque and gastric mucosa was observed. Positive correlation was obtained between the collected indices and quantity of H. pylori colonization.

  9. Lansoprazole increases serum IgG and IgM in H. pylori-infected patients.

    Science.gov (United States)

    Matsukawa, Y; Kurosaka, H; Kato, K; Hayashi, I; Minekawa, K; Arakawa, Y; Sawada, S

    2007-01-01

    Proton-pump inhibitors have been reported to influence the human immune system, we therefore evaluated the effect of lansoprazole, a proton-pump inhibitor, on humoral immunity. Patients with gastric ulcer received lansoprazole 30 mg/day for 8 weeks, and serum immunoglobulins were evaluated before and upon completion of the treatment. There were 79 patients with gastric ulcer; 51 were H. pylori-infected and 28 were H. pylori-uninfected. Eighteen patients positive for H. pylori were receiving at least one non-steroidal anti-inflammatory drug, and 12 patients negative for H. pylori received one non-steroidal anti-inflammatory drug. H. pylori-infected patients showed significant increases in serum immunoglobulins G and M 8 weeks after the start of lansoprazole treatment (PLansoprazole elevated serum levels of immunoglobulins G and M in gastric ulcer patients with H. pylori infection, particularly in those receiving non-steroidal anti-inflammatory drugs. Deducing from these observations, lansoprazole might alter the Th1 shift in the immune response induced by H. pylori infection.

  10. Enhanced M1 macrophage polarization in human helicobacter pylori-associated atrophic gastritis and in vaccinated mice.

    Directory of Open Access Journals (Sweden)

    Marianne Quiding-Järbrink

    Full Text Available BACKGROUND: Infection with Helicobacter pylori triggers a chronic gastric inflammation that can progress to atrophy and gastric adenocarcinoma. Polarization of macrophages is a characteristic of both cancer and infection, and may promote progression or resolution of disease. However, the role of macrophages and their polarization during H. pylori infection has not been well defined. METHODOLOGY/PRINCIPAL FINDINGS: By using a mouse model of infection and gastric biopsies from 29 individuals, we have analyzed macrophage recruitment and polarization during H. pylori infection by flow cytometry and real-time PCR. We found a sequential recruitment of neutrophils, eosinophils and macrophages to the gastric mucosa of infected mice. Gene expression analysis of stomach tissue and sorted macrophages revealed that gastric macrophages were polarized to M1 after H. pylori infection, and this process was substantially accelerated by prior vaccination. Human H. pylori infection was characterized by a mixed M1/M2 polarization of macrophages. However, in H. pylori-associated atrophic gastritis, the expression of inducible nitric oxide synthase was markedly increased compared to uncomplicated gastritis, indicative of an enhanced M1 macrophage polarization in this pre-malignant lesion. CONCLUSIONS/SIGNIFICANCE: These results show that vaccination of mice against H. pylori amplifies M1 polarization of gastric macrophages, and that a similar enhanced M1 polarization is present in human H. pylori-induced atrophic gastritis.

  11. Helicobacter pylori dwelling on the apical surface of gastrointestinal epithelium damages the mucosal barrier through direct contact.

    Science.gov (United States)

    Zhang, Chen; Zhang, Hongyu; Yu, Lu; Cao, Yi

    2014-10-01

    Epithelial junctions and mucins compose a major portion of the mucosal barrier. Helicobacter pylori (H. pylori) infections induce alterations of the tight junctions and adherens junctions in epithelial cells, although the precise mechanisms underlying this process are not fully understood. The expression of adhesion molecules and MUC1 was systematically investigated in gastrointestinal epithelial cells infected with H. pylori in vitro and in vivo. Furthermore, we developed several new in vitro methods to study the relationships between the bacterium and the dysfunction of tight junctions using Boyden Chambers. The expression of a series of junctional molecules and MUC1 decreased in the cultured cells that were infected with H. pylori. According to the degree of damage at the tight junctions, direct contact of H. pylori with the apical membrane of the cells resulted in the greatest increase in permeability compared to basal membrane binding or non-binding of H. pylori to the cells. Similarly, we noted that H. pylori infection could reduce the expression and glycosylation of MUC1. Helicobacter pylori dwelling on the apical surface of the gastrointestinal epithelium could directly induce serious injury of the mucosal barrier, and the new methods outlined here, based on the Boyden Chamber system, could be very useful for studying the relationships between bacteria and their target cells. © 2014 John Wiley & Sons Ltd.

  12. Pathogenesis of Helicobacter pylori infection

    Science.gov (United States)

    Sgouras, Dionyssios N.; Trang, Tran Thi Huyen; Yamaoka, Yoshio

    2015-01-01

    Three decades have passed since Warren and Marshall described the successful isolation and culture of Helicobacter pylori, the Gram-negative bacterium that colonizes the stomach of half the human population worldwide. Although it is documented that H. pylori infection is implicated in a range of disorders of the upper gastrointestinal tract, as well as associated organs, many aspects relating to host colonization, successful persistence and the pathophysiological mechanisms of this bacteria still remain controversial and are constantly being explored. Unceasing efforts to decipher the pathophysiology of H. pylori infection have illuminated the crucially important contribution of multifarious bacterial factors for H. pylori pathogenesis, in particular the cag pathogenicity island (PAI), the effector protein CagA and the vacuolating cytotoxin VacA. In addition, recent studies have provided insight into the importance of the gastrointestinal microbiota on the cumulative pathophysiology associated with H. pylori infections. This review focuses on the key findings of publications related to the pathogenesis of H. pylori infection published during the last year, with an emphasis on factors affecting colonization efficiency, cag PAI, CagA, VacA and gastrointestinal microbiota. PMID:26372819

  13. Comparative genomics of Helicobacter pylori

    Institute of Scientific and Technical Information of China (English)

    Quan-Jiang Dong; Qing Wang; Ying-Nin Xin; Ni Li; Shi-Ying Xuan

    2009-01-01

    Genomic sequences have been determined for a number of strains of Helicobacter pylori (H pylori) and related bacteria.With the development of microarray analysis and the wide use of subtractive hybridization techniques,comparative studies have been carried out with respect to the interstrain differences between H pylori and inter-species differences in the genome of related bacteria.It was found that the core genome of H pylori constitutes 1111 genes that are determinants of the species properties.A great pool of auxillary genes are mainly from the categories of cag pathogenicity islands,outer membrane proteins,restriction-modification system and hypothetical proteins of unknown function.Persistence of H pylori in the human stomach leads to the diversification of the genome.Comparative genomics suggest that a host jump has occurs from humans to felines.Candidate genes specific for the development of the gastric diseases were identified.With the aid of proteomics,population genetics and other molecular methods,future comparative genomic studies would dramatically promote our understanding of the evolution,pathogenesis and microbiology of H pylori.

  14. Helicobacter pylori in gastric carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Hyo; Jun; Ahn; Dong; Soo; Lee

    2015-01-01

    Gastric cancer still is a major concern as the third most common cancer worldwide, despite declining rates of incidence in many Western countries. Helicobacter pylori(H. pylori) is the major cause of gastric carcinogenesis, and its infection insults gastric mucosa leading to theoccurrence of atrophic gastritis which progress to intestinal metaplasia, dysplasia, early gastric cancer, and advanced gastric cancer consequently. This review focuses on multiple factors including microbial virulence factors, host genetic factors, and environmental factors, which can heighten the chance of occurrence of gastric adenocarcinoma due to H. pylori infection. Bacterial virulence factors are key components in controlling the immune response associated with the induction of carcinogenesis, and cag A and vac A are the most well-known pathogenic factors. Host genetic polymorphisms contribute to regulating the inflammatory response to H. pylori and will become increasingly important with advancing techniques. Environmental factors such as high salt and smoking may also play a role in gastric carcinogenesis. It is important to understand the virulence factors, host genetic factors, and environmental factors interacting in the multistep process of gastric carcinogenesis. To conclude, prevention via H. pylori eradication and controlling environmental factors such as diet, smoking, and alcohol is an important strategy to avoid H. pylori-associated gastric carcinogenesis.

  15. Does Helicobacter pylori affect portal hypertensive gastropathy?

    Directory of Open Access Journals (Sweden)

    Al Mofleh Ibrahim

    2007-01-01

    Full Text Available Helicobacter pylori (H. pylori is a major etiological factor of peptic ulcer disease (PUD. It is supposed to be a risk factor for the more frequently encountered PUD in patients with liver cirrhosis. Several investigators have evaluated the effect of H. pylori on liver cirrhosis, portal hypertensive gastropathy (PHG and encephalopathy with controversial results. Some reports have shown a higher seroprevalence and suggested a synergistic effect of H. pylori on liver cirrhosis and PHG. However, this increased prevalence is associated with a negative histology and is not influenced by the cause of cirrhosis, PHG, Child class or gender. Most studies have not found any correlation between H. pylori and PHG. In contrast, other studies have reported a markedly lower prevalence of H. pylori in cirrhotics with duodenal ulcer compared to controls. The aim of this article is to review the relationship between H. pylori infection and portal hypertensive gastropathy and the role of H. pylori eradication in cirrhotic patients.

  16. Helicobacter pylori infection- recent developments in diagnosis

    National Research Council Canada - National Science Library

    Ana Isabel Lopes Filipa F Vale Mónica Oleastro

    2014-01-01

    Considering the recommended indications for Helicobacter pylori(H.pylori)eradication therapy and the broad spectrum of available diagnostic methods,a reliable diagnosis is mandatory both before and after eradication...

  17. What Do We Do about Helicobacter pylori?

    Directory of Open Access Journals (Sweden)

    CJ Hawkey

    1999-01-01

    Full Text Available Heliobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs cause ulcers by different mechanisms. Under some circumstances, patients infected with H pylori may be less prone to NSAID-associated ulcers than those who are H pylori-negative. Eradication trials have yielded differing results. However, those who have studied patients who have a past history of ulcer disease and are already established on NSAIDs have shown no benefit from H pylori eradication.

  18. Non-pharmacological treatment of Helicobacter pylori

    Institute of Scientific and Technical Information of China (English)

    Haim Shmuely; Noam Domniz; Jacob Yahav

    2016-01-01

    Many food and plant extracts have shown in vitro antiHelicobacter pylori(H.pylori)activity,but are less effective in vivo.The anti-H.pylori effects of these extracts are mainly permeabilitization of the membrane,anti-adhesion,inhibition of bacterial enzymes andbacterial grown.We,herein,review treatment effects of cranberry,garlic,curcumin,ginger and pistacia gum against H.pylori in both in vitro,animal studies and in vivo studies.

  19. The Importance of Toll-like Receptors in NF-κB Signaling Pathway Activation by Helicobacter pylori Infection and the Regulators of this Response.

    Science.gov (United States)

    Hu, Yi; Liu, Jian-Ping; Zhu, Yin; Lu, Nong-Hua

    2016-10-01

    Helicobacter pylori (H. pylori) is a common pathogenic bacterium in the stomach that infects almost half of the population worldwide and is closely related to gastric diseases and some extragastric diseases, including iron-deficiency anemia and idiopathic thrombocytopenic purpura. Both the Maastricht IV/Florence consensus report and the Kyoto global consensus report have proposed the eradication of H. pylori to prevent gastric cancer as H.pylori has been shown to be a major cause of gastric carcinogenesis. The interactions between H. pylori and host receptors induce the release of the proinflammatory cytokines by activating proinflammatory signaling pathways such as nuclear factor kappa B (NF-κB), which plays a central role in inflammation, immune response, and carcinogenesis. Among these receptors, Toll-like receptors (TLRs) are classical pattern recognition receptors in the recognition of H. pylori and the mediation of the host inflammatory and immune responses to H. pylori. TLR polymorphisms also contribute to the clinical consequences of H. pylori infection. In this review, we focus on the functions of TLRs in the NF-κB signaling pathway activated by H. pylori, the regulators modulating this response, and the functions of TLR polymorphisms in H.pylori-related diseases.

  20. Helicobacter pylori Seropositivity in Children With Asthma

    OpenAIRE

    Yousefichaijan; Mosayebi; Sharafkhah; Kahbazi; Heydarbagi; Rafiei

    2016-01-01

    Background Some studies have reported an association between Helicobacter pylori (H. pylori) colonization and the occurrence of asthma or other allergies. However, data are inconsistent, and few studies have been performed in children. Objectives The current study aimed to investigate H. pylori seropositivity in children with and without asthma. Patients and Methods This cross-sect...

  1. Elevated interleukin-32 expression is associated with Helicobacter pylori-related gastritis.

    Directory of Open Access Journals (Sweden)

    Liu-Sheng Peng

    Full Text Available BACKGROUND: Interleukin-32 (IL-32 is a recently discovered proinflammatory cytokine involved in inflammatory diseases. We investigated the expression of IL-32 and its regulation mechanism in the inflammatory response of patients with Helicobacter pylori (H. pylori infection. DESIGN AND METHODS: IL-32 mRNA and protein expression in gastric tissues was detected by quantitative real-time PCR and immunohistochemistry. The regulation of IL-32 in human gastric epithelia cell line AGS was investigated by different cytokine stimulation and different H. pylori strain infection. RESULTS: Gastric IL-32 mRNA and protein expression were elevated in patients with H. pylori infection and positively correlated with gastritis. In H. pylori-infected patients, the mRNA level of IL-32 was also correlated with that of proinflammatory cytokines IL-1β and TNF-α. In vitro IL-1β and TNF-α could upregulate IL-32 mRNA and protein level in AGS cells, which was dependent on NF-κB signal pathway. The regulation of IL-32 expression in response to H. pylori-infection could be weakened by using neutralizing antibodies to block IL-1β and TNF-α. Moreover, H. pylori-infected AGS cells also induced IL-32 mRNA and protein expression, which was dependent on CagA. CONCLUSIONS: IL-32 level is elevated in patients with H. pylori infection and its expression is regulated by proinflammatory stimuli, suggesting that IL-32 may play a role in the pathogenesis of H. pylori-related gastritis.

  2. Comparative Analysis of the Interaction of Helicobacter pylori with Human Dendritic Cells, Macrophages, and Monocytes

    Science.gov (United States)

    Fehlings, Michael; Drobbe, Lea; Moos, Verena; Renner Viveros, Pablo; Hagen, Jana; Beigier-Bompadre, Macarena; Pang, Ervinna; Belogolova, Elena; Churin, Yuri; Schneider, Thomas; Meyer, Thomas F.; Aebischer, Toni

    2012-01-01

    Helicobacter pylori may cause chronic gastritis, gastric cancer, or lymphoma. Myeloid antigen-presenting cells (APCs) are most likely involved in the induction and expression of the underlying inflammatory responses. To study the interaction of human APC subsets with H. pylori, we infected monocytes, monocyte-derived dendritic cells (DCs), and monocyte-derived (classically activated; M1) macrophages with H. pylori and analyzed phenotypic alterations, cytokine secretion, phagocytosis, and immunostimulation. Since we detected CD163+ (alternatively activated; M2) macrophages in gastric biopsy specimens from H. pylori-positive patients, we also included monocyte-derived M2 macrophages in the study. Upon H. pylori infection, monocytes secreted interleukin-1β (IL-1β), IL-6, IL-10, and IL-12p40 (partially secreted as IL-23) but not IL-12p70. Infected DCs became activated, as shown by the enhanced expression of CD25, CD80, CD83, PDL-1, and CCR7, and secreted IL-1β, IL-6, IL-10, IL-12p40, IL-12p70, and IL-23. However, infection led to significantly downregulated CD209 and suppressed the constitutive secretion of macrophage migration inhibitory factor (MIF). H. pylori-infected M1 macrophages upregulated CD14 and CD32, downregulated CD11b and HLA-DR, and secreted mainly IL-1β, IL-6, IL-10, IL-12p40, and IL-23. Activation of DCs and M1 macrophages correlated with increased capacity to induce T-cell proliferation and decreased phagocytosis of dextran. M2 macrophages upregulated CD14 and CD206 and secreted IL-10 but produced less of the proinflammatory cytokines than M1 macrophages. Thus, H. pylori affects the functions of human APC subsets differently, which may influence the course and the outcome of H. pylori infection. The suppression of MIF in DCs constitutes a novel immune evasion mechanism exploited by H. pylori. PMID:22615251

  3. Helicobacter pylori colonization ameliorates glucose homeostasis in mice through a PPAR γ-dependent mechanism.

    Directory of Open Access Journals (Sweden)

    Josep Bassaganya-Riera

    Full Text Available BACKGROUND: There is an inverse secular trend between the incidence of obesity and gastric colonization with Helicobacter pylori, a bacterium that can affect the secretion of gastric hormones that relate to energy homeostasis. H. pylori strains that carry the cag pathogenicity island (PAI interact more intimately with gastric epithelial cells and trigger more extensive host responses than cag(- strains. We hypothesized that gastric colonization with H. pylori strains differing in cag PAI status exert distinct effects on metabolic and inflammatory phenotypes. METHODOLOGY/PRINCIPAL FINDINGS: To test this hypothesis, we examined metabolic and inflammatory markers in db/db mice and mice with diet-induced obesity experimentally infected with isogenic forms of H. pylori strain 26695: the cag PAI wild-type and its cag PAI mutant strain 99-305. H. pylori colonization decreased fasting blood glucose levels, increased levels of leptin, improved glucose tolerance, and suppressed weight gain. A response found in both wild-type and mutant H. pylori strain-infected mice included decreased white adipose tissue macrophages (ATM and increased adipose tissue regulatory T cells (Treg cells. Gene expression analyses demonstrated upregulation of gastric PPAR γ-responsive genes (i.e., CD36 and FABP4 in H. pylori-infected mice. The loss of PPAR γ in immune and epithelial cells in mice impaired the ability of H. pylori to favorably modulate glucose homeostasis and ATM infiltration during high fat feeding. CONCLUSIONS/SIGNIFICANCE: Gastric infection with some commensal strains of H. pylori ameliorates glucose homeostasis in mice through a PPAR γ-dependent mechanism and modulates macrophage and Treg cell infiltration into the abdominal white adipose tissue.

  4. [Helicobacter pylori morphological forms and their potential role in the transmission of infection].

    Science.gov (United States)

    Rudnicka, Karolina; Graczykowski, Maciej; Tenderenda, Michał; Chmiela, Magdalena

    2014-03-04

    More than 50% of the world's population is infected with Helicobacter pylori (H. pylori) - a Gram negative bacterium, which persists in the human stomach and duodenum, causing gastric or duodenal ulcers and gastric cancer. The majority of H. pylori cells demonstrate rod-shape morphology occurring in two subtypes: spiral and S-shaped. Both are isolated from mucus layer biopsy specimens of the stomach or from short-term cultures. However, results obtained from electron microscopy revealed that H. pylori long-term cultures not only consist of classic, spiral shaped bacteria, but also contain alternative forms of coccoid cells. Further investigations showed that coccoid forms of H. pylori may be divided into two types: viable but non-culturable coccus (VBnC) and a degenerative form, coccoid stage which is probably the effect of bacterial cell death. Transformation from spiral to coccoid form is induced under stress conditions, such as the presence of antibiotics. But still there is no evidence for reversion from the coccoid state to the viable and infectious spiral form. Besides the planktonic form, H. pylori also forms homo-, and heterogenic biofilms, which may constitute a potential environmental reservoir of this bacterium. The antigenic repertoire and the immunomodulatory and infectious properties of different H. pylori forms differ greatly. The variation in those properties suggests that morphological forms of H. pylori are potentially involved in the transmission of the infection. This review presents recent findings on the variability, antigenicity and infectious properties of H. pylori morphological forms and their potential role in the transmission of the infection.

  5. Helicobacter pylori morphological forms and their potential role in the transmission of infection

    Directory of Open Access Journals (Sweden)

    Karolina Rudnicka,

    2014-03-01

    Full Text Available More than 50% of the world’s population is infected with Helicobacter pylori (H. pylori – a Gram negative bacterium, which persists in the human stomach and duodenum, causing gastric or duodenal ulcers and gastric cancer. The majority of H. pylori cells demonstrate rod-shape morphology occurring in two subtypes: spiral and S-shaped. Both are isolated from mucus layer biopsy specimens of the stomach or from short-term cultures. However, results obtained from electron microscopy revealed that H. pylori long-term cultures not only consist of classic, spiral shaped bacteria, but also contain alternative forms of coccoid cells. Further investigations showed that coccoid forms of H. pylori may be divided into two types: viable but non-culturable coccus (VBnC and a degenerative form, coccoid stage which is probably the effect of bacterial cell death. Transformation from spiral to coccoid form is induced under stress conditions, such as the presence of antibiotics. But still there is no evidence for reversion from the coccoid state to the viable and infectious spiral form. Besides the planktonic form, H. pylori also forms homo-, and heterogenic biofilms, which may constitute a potential environmental reservoir of this bacterium. The antigenic repertoire and the immunomodulatory and infectious properties of different H. pylori forms differ greatly. The variation in those properties suggests that morphological forms of H. pylori are potentially involved in the transmission of the infection. This review presents recent findings on the variability, antigenicity and infectious properties of H. pylori morphological forms and their potential role in the transmission of the infection.

  6. A pro-inflammatory role for Th22 cells in Helicobacter pylori-associated gastritis.

    Science.gov (United States)

    Zhuang, Yuan; Cheng, Ping; Liu, Xiao-fei; Peng, Liu-sheng; Li, Bo-sheng; Wang, Ting-ting; Chen, Na; Li, Wen-hua; Shi, Yun; Chen, Weisan; Pang, Ken C; Zeng, Ming; Mao, Xu-hu; Yang, Shi-ming; Guo, Hong; Guo, Gang; Liu, Tao; Zuo, Qian-fei; Yang, Hui-jie; Yang, Liu-yang; Mao, Fang-yuan; Lv, Yi-pin; Zou, Quan-ming

    2015-09-01

    Helper T (Th) cell responses are critical for the pathogenesis of Helicobacter pylori-induced gastritis. Th22 cells represent a newly discovered Th cell subset, but their relevance to H. pylori-induced gastritis is unknown. Flow cytometry, real-time PCR and ELISA analyses were performed to examine cell, protein and transcript levels in gastric samples from patients and mice infected with H. pylori. Gastric tissues from interleukin (IL)-22-deficient and wild-type (control) mice were also examined. Tissue inflammation was determined for pro-inflammatory cell infiltration and pro-inflammatory protein production. Gastric epithelial cells and myeloid-derived suppressor cells (MDSC) were isolated, stimulated and/or cultured for Th22 cell function assays. Th22 cells accumulated in gastric mucosa of both patients and mice infected with H. pylori. Th22 cell polarisation was promoted via the production of IL-23 by dendritic cells (DC) during H. pylori infection, and resulted in increased inflammation within the gastric mucosa. This inflammation was characterised by the CXCR2-dependent influx of MDSCs, whose migration was induced via the IL-22-dependent production of CXCL2 by gastric epithelial cells. Under the influence of IL-22, MDSCs, in turn, produced pro-inflammatory proteins, such as S100A8 and S100A9, and suppressed Th1 cell responses, thereby contributing to the development of H. pylori-associated gastritis. This study, therefore, identifies a novel regulatory network involving H. pylori, DCs, Th22 cells, gastric epithelial cells and MDSCs, which collectively exert a pro-inflammatory effect within the gastric microenvironment. Efforts to inhibit this Th22-dependent pathway may therefore prove a valuable strategy in the therapy of H. pylori-associated gastritis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  7. Piperine treatment suppresses Helicobacter pylori toxin entry in to gastric epithelium and minimizes β-catenin mediated oncogenesis and IL-8 secretion in vitro.

    Science.gov (United States)

    Tharmalingam, Nagendran; Park, Min; Lee, Min Ho; Woo, Hyun Jun; Kim, Hyun Woo; Yang, Ji Yeong; Rhee, Ki-Jong; Kim, Jong-Bae

    2016-01-01

    Helicobacter pylori related gastric cancer initiation has been studied widely. The objective of our present study was to evaluate the effect of a single compound piperine on H. pylori infection and its anti-inflammatory and anti-cancer effects in vitro. Cytotoxicity was tested by Ez-cytox cell viability assay kit. Effects of piperine on H. pylori toxin gene expression and IL-8 expression in mammalian cells during infection were assessed by RT-PCR. Effects of piperine on toxin entry into host cells, E-cadherin cleavage by H. pylori, and the changes in H. pylori mediated β-catenin expression and IL-8 secretion were determined by immunoblotting. Piperine treatment restrained the entry of CagA and VacA into AGS cells. Piperine administration in H. pylori infection reduced E-cadherin cleavage in stomach epithelium. In addition, H. pylori induced β-catenin up-regulation was reduced. Piperine administration impaired IL-8 secretion in H. pylori-infected gastric epithelial cells. As we reported previously piperine restrained H. pylori motility. The possible reason behind the H. pylori inhibition mechanism of piperine could be the dwindled motility, which weakened H. pylori adhesion to gastric epithelial cells. The reduced adhesion decreased the toxin entry thereby secreting less amount of IL-8. In addition, piperine treatment suppressed H. pylori protease led to reduction of E-cadherin cleavage and β-catenin expression resulting in diminished β-catenin translocation into the nucleus thus decreasing the risk of oncogenesis. To our knowledge, this is the preliminary report of piperine mediated H. pylori infection control on gastric epithelial cells in-vitro.

  8. Inverse Relationship Between Helicobacter Pylori Infection and Asthma Among Adults Younger than 40 Years: A Cross-Sectional Study.

    Science.gov (United States)

    Lim, Joo Hyun; Kim, Nayoung; Lim, Seon Hee; Kwon, Jin-Won; Shin, Cheol Min; Chang, Yoon-Seok; Kim, Joo Sung; Jung, Hyun Chae; Cho, Sang-Heon

    2016-02-01

    Recent studies have suggested that Helicobacter pylori could prevent allergic disease, particularly in children. However, whether this is true in adults is controversial. The aim of this study was to investigate whether there is negative association between H. pylori infection and asthma among adults in an area with a high prevalence of H. pylori.This was a cross-sectional study using 2011 health surveillance data. Blood samples were taken from all participants to measure serum H. pylori IgG status. Information on demographics, socioeconomic status, and medical history, including asthma and other allergic conditions were collected by a questionnaire.Of the 15,032 patients, 9492 (63.1%) had a history of H. pylori infection, 359 (2.4%) had asthma, and 3277 (21.8%) had other allergic conditions. H. pylori infection was positively correlated with age (OR, 1.050; 95% CI, 1.047-1.053, P Asthma history was positively correlated with age (OR, 1.022; 95% CI, 1.013-1.032, P asthma in the total participants (OR, 1.041; 95% CI, 1.021-1.062, P asthma (OR, 0.503; 95% CI, 0.280-0.904, P = 0.021). Other allergic conditions were not related with H. pylori infection among the total and those asthma among young adults suggests that the underlying immune mechanism induced by H. pylori infection may affect allergic reactions associated with asthma in young adults.

  9. Cell-cycle inhibition by Helicobacter pylori L-asparaginase.

    Directory of Open Access Journals (Sweden)

    Claudia Scotti

    Full Text Available Helicobacter pylori (H. pylori is a major human pathogen causing chronic gastritis, peptic ulcer, gastric cancer, and mucosa-associated lymphoid tissue lymphoma. One of the mechanisms whereby it induces damage depends on its interference with proliferation of host tissues. We here describe the discovery of a novel bacterial factor able to inhibit the cell-cycle of exposed cells, both of gastric and non-gastric origin. An integrated approach was adopted to isolate and characterise the molecule from the bacterial culture filtrate produced in a protein-free medium: size-exclusion chromatography, non-reducing gel electrophoresis, mass spectrometry, mutant analysis, recombinant protein expression and enzymatic assays. L-asparaginase was identified as the factor responsible for cell-cycle inhibition of fibroblasts and gastric cell lines. Its effect on cell-cycle was confirmed by inhibitors, a knockout strain and the action of recombinant L-asparaginase on cell lines. Interference with cell-cycle in vitro depended on cell genotype and was related to the expression levels of the concurrent enzyme asparagine synthetase. Bacterial subcellular distribution of L-asparaginase was also analysed along with its immunogenicity. H. pylori L-asparaginase is a novel antigen that functions as a cell-cycle inhibitor of fibroblasts and gastric cell lines. We give evidence supporting a role in the pathogenesis of H. pylori-related diseases and discuss its potential diagnostic application.

  10. Cell-Cycle Inhibition by Helicobacter pylori L-Asparaginase

    Science.gov (United States)

    Scotti, Claudia; Sommi, Patrizia; Pasquetto, Maria Valentina; Cappelletti, Donata; Stivala, Simona; Mignosi, Paola; Savio, Monica; Chiarelli, Laurent Roberto; Valentini, Giovanna; Bolanos-Garcia, Victor M.; Merrell, Douglas Scott; Franchini, Silvia; Verona, Maria Luisa; Bolis, Cristina; Solcia, Enrico; Manca, Rachele; Franciotta, Diego; Casasco, Andrea; Filipazzi, Paola; Zardini, Elisabetta; Vannini, Vanio

    2010-01-01

    Helicobacter pylori (H. pylori) is a major human pathogen causing chronic gastritis, peptic ulcer, gastric cancer, and mucosa-associated lymphoid tissue lymphoma. One of the mechanisms whereby it induces damage depends on its interference with proliferation of host tissues. We here describe the discovery of a novel bacterial factor able to inhibit the cell-cycle of exposed cells, both of gastric and non-gastric origin. An integrated approach was adopted to isolate and characterise the molecule from the bacterial culture filtrate produced in a protein-free medium: size-exclusion chromatography, non-reducing gel electrophoresis, mass spectrometry, mutant analysis, recombinant protein expression and enzymatic assays. L-asparaginase was identified as the factor responsible for cell-cycle inhibition of fibroblasts and gastric cell lines. Its effect on cell-cycle was confirmed by inhibitors, a knockout strain and the action of recombinant L-asparaginase on cell lines. Interference with cell-cycle in vitro depended on cell genotype and was related to the expression levels of the concurrent enzyme asparagine synthetase. Bacterial subcellular distribution of L-asparaginase was also analysed along with its immunogenicity. H. pylori L-asparaginase is a novel antigen that functions as a cell-cycle inhibitor of fibroblasts and gastric cell lines. We give evidence supporting a role in the pathogenesis of H. pylori-related diseases and discuss its potential diagnostic application. PMID:21085483

  11. Inflammation, Immunity, and Vaccines for Helicobacter pylori Infection.

    Science.gov (United States)

    Walduck, Anna; Andersen, Leif P; Raghavan, Sukanya

    2015-09-01

    During the last year, a variety of studies have been published that increases our understanding of the basic mechanisms of immunity and inflammation in Helicobacter pylori infection and progression to gastric cancer. Innate immune regulation and epithelial cell response were covered by several studies that contribute with new insights in the host response to H. pylori infection. Also, the adaptive immune response to H. pylori and particularly the role of IL-22 have been addressed in some studies. These advances may improve vaccine development where new strategies have been published. Two major studies analyzed H. pylori genomes of 39 worldwide strains and looked at the protein profiles. In addition, multi-epitope vaccines for therapeutic use have been investigated. Studies on different adjuvants and delivery systems have also given us new insights. This review presents articles from the last year that reveal detailed insight into immunity and regulation of inflammation, the contribution of immune cells to the development of gastric cancer, and understanding mechanisms of vaccine-induced protection. © 2015 John Wiley & Sons Ltd.

  12. Helicobacter pylori filtrate impairs spatial learning and memory in rats and increases β-amyloid by enhancing expression of presenilin-2

    Directory of Open Access Journals (Sweden)

    Xiu-Lian eWang

    2014-04-01

    Full Text Available Helicobacter pylori (H.pylori infection is related with a high risk of Alzheimer’s Disease (AD, but the intrinsic link between H.pylori infection and AD development is still missing. In the present study, we explored the effect of H.pylori infection on cognitive function and β-amyloid production in rats. We found that intraperitoneal injection of H.pylori filtrate induced spatial learning and memory deficit in rats with a simultaneous retarded dendritic spine maturation in hippocampus. Injection of H.pylori filtrate significantly increased Aβ42 both in the hippocampus and cortex, together with an increased level of presenilin-2 (PS-2, one key component of γ-secretase involved in Aβ production. Incubation of H.pylori filtrate with N2a cells which over-express APP also resulted in increased PS-2 expression and Aβ42 overproduction. Injection of Escherichia coli (E.coli filtrate, another common intestinal bacterium, had no effect on cognitive function in rats and Aβ production in rats and cells. These data suggest a specific effect of H.pylori on cognition and Aβ production. We conclude that soluble surface fractions of H.pylori may promote Aβ42 formation by enhancing the activity of γ-secretase, thus induce cognitive impairment through interrupting the synaptic function.

  13. VCP phosphorylation-dependent interaction partners prevent apoptosis in Helicobacter pylori-infected gastric epithelial cells.

    Directory of Open Access Journals (Sweden)

    Cheng-Chou Yu

    Full Text Available Previous studies have demonstrated that valosin-containing protein (VCP is associated with H. pylori-induced gastric carcinogenesis. By identifying the interactome of VCP overexpressed in AGS cells using a subtractive proteomics approach, we aimed to characterize the cellular responses mediated by VCP and its functional roles in H. pylori-associated gastric cancer. VCP immunoprecipitations followed by proteomic analysis identified 288 putative interacting proteins, 18 VCP-binding proteins belonged to the PI3K/Akt signaling pathway. H. pylori infection increased the interaction between Akt and VCP, Akt-dependent phosphorylation of VCP, levels of ubiquitinated proteins, and aggresome formation in AGS cells. Furthermore, phosphorylated VCP co-localized with the aggresome, bound ubiquitinated proteins, and increased the degradation of cellular regulators to protect H. pylori-infected AGS cells from apoptosis. Our study demonstrates that VCP phosphorylation following H. pylori infection promotes both gastric epithelial cell survival, mediated by the PI3K/Akt pathway, and the degradation of cellular regulators. These findings provide novel insights into the mechanisms of H. pylori infection induced gastric carcinogenesis.

  14. Helicobacter pylori upregulates the expression of p16(INK4) in gastric cancer cells.

    Science.gov (United States)

    Wang, Ping; Mei, Juan; Zhang, Ning; Tao, Jing; Tian, Hua; Fu, Guo-Hui

    2011-01-01

    Previous studies have suggested that p16(INK4) protein is over expressed in gastric cancer. However, whether H. pylori infection induces p16(INK4) in human gastric epithelial cells remains to be determined. The aim of this study was to analyze the molecular mechanism of H. pylori-induced p16(INK4) expression. Expression of p16(INK4) mRNA and Sp1 mRNA were assessed by reverse transcription-PCR. Expression of p16(INK4) protein was assessed by Western blot and immunocytochemistry. A luciferase assay was used to monitor activation of the p16(INK4) gene promoter and to explore the binding of transcription factors to this promoter. H. pylori upregulates the expression of p16(INK4) in gastric cancer SGC7901 cells. p16 promoter is highly actived in SGC7901 cells by H. pylori. Sp1 activates the expression of p16(INK4)-Luc and promotes the protein level of p16(INK4). H. pylori upregulates the expression of p16(INK4) in gastric cancer SGC7901 cells via the p16(INK4) promoter, and Sp1 is involved in the activation of p16(INK4) promoter by H. pylori.

  15. Interplay of the Gastric Pathogen Helicobacter pylori with Toll-Like Receptors

    Directory of Open Access Journals (Sweden)

    Suneesh Kumar Pachathundikandi

    2015-01-01

    Full Text Available Toll-like receptors (TLRs are crucial for pathogen recognition and downstream signaling to induce effective immunity. The gastric pathogen Helicobacter pylori is a paradigm of persistent bacterial infections and chronic inflammation in humans. The chronicity of inflammation during H. pylori infection is related to the manipulation of regulatory cytokines. In general, the early detection of H. pylori by TLRs and other pattern recognition receptors (PRRs is believed to induce a regulatory cytokine or chemokine profile that eventually blocks the resolution of inflammation. H. pylori factors such as LPS, HSP-60, NapA, DNA, and RNA are reported in various studies to be recognized by specific TLRs. However, H. pylori flagellin evades the recognition of TLR5 by possessing a conserved N-terminal motif. Activation of TLRs and resulting signal transduction events lead to the production of pro- and anti-inflammatory mediators through activation of NF-κB, MAP kinases, and IRF signaling pathways. The genetic polymorphisms of these important PRRs are also implicated in the varied outcome and disease progression. Hence, the interplay of TLRs and bacterial factors highlight the complexity of innate immune recognition and immune evasion as well as regulated processes in the progression of associated pathologies. Here we will review this important aspect of H. pylori infection.

  16. Helicobacter pylori and Its Virulence Factors' Effect on Serum Oxidative DNA Damages in Adults With Dyspepsia

    Directory of Open Access Journals (Sweden)

    Heshmat Shahi

    2016-12-01

    Full Text Available Helicobacter Pylori infection is a common gastrointestinal infection that can cause pathological effects, increase oxidative stress and induce an inflammatory response in gastric mucosa. Inflammatory aspects may prompt the production of radical oxygen substance (ROS which may damage cells and release 8-hydroxydyoxyguanosine (8-OHdG to serum. In this study, we evaluate the prevalence of H. pylori virulence factors and the association between serum level of 8-OHdG, H. pylori infection, and its various virulence factors. The presence of H. pylori and prevalence of cagA, babA and oipA genes in samples were determined by rapid urease test (RUT, histopathological exam (HE and polymerase chain reaction (PCR and oxidative DNA damage situation were assessed by using serum level of 8-OHdG. There was not any direct relation between H. pylori negative and H. pylori oipA+specimens by 8-OHdG serum level (P>0.05. In all clinical observations, the presence of cagA and oipA genes was common. There was a statistical relationship between the presence of cagA, babA factors, and high serum level of 8-OHdG (P<0.05. The presence of cagA and babA virulence factors may be associated with increased serum 8-OHdG in dyspeptic patients and may induce the damage to gastric cells.

  17. Helicobacter pylori and Its Virulence Factors' Effect on Serum Oxidative DNA Damages in Adults With Dyspepsia.

    Science.gov (United States)

    Shahi, Heshmat; Bahreiny, Rasoul; Reiisi, Somayeh

    2016-11-01

    Helicobacter Pylori infection is a common gastrointestinal infection that can cause pathological effects, increase oxidative stress and induce an inflammatory response in gastric mucosa. Inflammatory aspects may prompt the production of radical oxygen substance (ROS) which may damage cells and release 8-hydroxydyoxyguanosine (8-OHdG) to serum. In this study, we evaluate the prevalence of H. pylori virulence factors and the association between serum level of 8-OHdG, H. pylori infection, and its various virulence factors. The presence of H. pylori and prevalence of cagA, babA and oipA genes in samples were determined by rapid urease test (RUT), histopathological exam (HE) and polymerase chain reaction (PCR) and oxidative DNA damage situation were assessed by using serum level of 8-OHdG. There was not any direct relation between H. pylori negative and H. pylori oipA+specimens by 8-OHdG serum level (P>0.05). In all clinical observations, the presence of cagA and oipA genes was common. There was a statistical relationship between the presence of cagA, babA factors, and high serum level of 8-OHdG (P<0.05). The presence of cagA and babA virulence factors may be associated with increased serum 8-OHdG in dyspeptic patients and may induce the damage to gastric cells.

  18. Epidemiology of Helicobacter pylori infection.

    Science.gov (United States)

    Leja, Mārcis; Axon, Anthony; Brenner, Hermann

    2016-09-01

    This review of recent publications related to the epidemiology of Helicobacter pylori highlights the origin of the infection, its changing prevalence, transmission, and outcome. A number of studies have addressed the ancestor roots of the bacteria, and the first genomewide analysis of bacterial strains suggests that its coexistence with humans is more ancient than previously thought. As opposed to the generally declining prevalence of H. pylori (including China and Japan), in Sweden, the prevalence of atrophic gastritis in the young population has risen. The prevalence of the infection remains high in the indigenous populations of the Arctic regions, and reinfection rates are high. A high prevalence is permanently found in the Siberian regions of Russia as well. Several studies, some of which used multiplex serology, addressed prevalence of and risks associated with various H. pylori serotypes, thereby enabling more precise risk assessment. Transmission of H. pylori was discussed, specifically fecal-oral transmission and the use of well-water and other unpurified water. Finally, the long-term course of H. pylori infection was considered, with an estimated 89% of noncardia gastric cancer cases being attributable to the infection. © 2016 John Wiley & Sons Ltd.

  19. Helicobacter pylori infection and skin disorders.

    Science.gov (United States)

    Kutlubay, Zekayi; Zara, Tuba; Engin, Burhan; Serdaroğlu, Server; Tüzün, Yalçin; Yilmaz, Erkan; Eren, Bülent

    2014-08-01

    Helicobacter pylori is a Gram-negative bacterium that has been linked to peptic ulcer disease, gastric lymphoma, and gastric carcinoma. Apart from its well-demonstrated role in gastroduodenal diseases, some authors have suggested a potential role of Helicobacter pylori infection in several extra-intestinal pathologies including haematological, cardiovascular, neurological, metabolic, autoimmune, and dermatological diseases. Some studies suggest an association between Helicobacter pylori infection and skin diseases such as chronic idiopathic urticaria and rosacea. There have also been few case reports documenting association between Helicobacter pylori and psoriasis vulgaris, Behçet's disease, alopecia areata, Henoch-Schönlein purpura, and Sweet's syndrome. However, more systematic studies are required to clarify the proposed association between Helicobacter pylori and skin diseases; most of the studies do not show relevant relationships of these diseases with Helicobacter pylori infections. This review discusses skin diseases that are believed to be associated with Helicobacter pylori.

  20. Dietary prevention of Helicobacter pylori-associated gastric cancer with kimchi.

    Science.gov (United States)

    Jeong, Migyeong; Park, Jong-Min; Han, Young-Min; Park, Kun Young; Lee, Don Haeng; Yoo, Joon-Hwan; Cho, Joo Young; Hahm, Ki-Baik

    2015-10-06

    To prove whether dietary intervention can prevent Helicobacter pylori-induced atrophic gastritis and gastric cancer, we developed cancer preventive kimchi (cpKimchi) through special recipe and administered to chronic H. pylori-initiated, high salt diet-promoted, gastric tumorigenesis mice model. H. pylori-infected C57BL/6 mice were administered with cpKimchi mixed in drinking water up to 36 weeks. Gross and pathological gastric lesions were evaluated after 24 and 36 weeks, respectively and explored underlying molecular changes to explain efficacies. Cancer preventive actions of anti-inflammation and anti-mutagenesis were compared between standard recipe kimchi (sKimchi) and special recipe cpKimchi in in vitro H. pylori-infected cell model. The erythematous and nodular changes, mucosal ulcerative and erosive lesions in the stomach were noted at 24th weeks, but cpKimchi administration significantly ameliorated. After 36th weeks, scattered nodular masses, some ulcers, and thin nodular gastric mucosa were noted in H. pylori-infected mice, whereas these gross lesions were significantly attenuated in cpKimchi group. On molecular analysis, significant expressions of COX-2 and IL-6, activated NF-κB and STAT3, increased apoptosis, and marked oxidative stresses were noted in H. pylori-infected group relevant to tumorigenesis, but these were all significantly attenuated in cpKimchi group. cpKimchi extracts imparted significant selective induction of apoptosis only in cancer cells, led to inhibition of H. pylori-induced proliferation, while no cytotoxicity through significant HO-1 induction in non-transformed gastric cells. In conclusion, daily dietary intake of cpKimchi can be an effective way either to rejuvenate H. pylori-atrophic gastritis or to prevent tumorigenesis supported with the concerted actions of anti-oxidative, anti-inflammatory, and anti-mutagenic mechanisms.

  1. Helicobacter pylori Outer Membrane Protein 18 (Hp1125 Is Involved in Persistent Colonization by Evading Interferon-γ Signaling

    Directory of Open Access Journals (Sweden)

    Yuqun Shan

    2015-01-01

    Full Text Available Outer membrane proteins (OMPs can induce an immune response. Omp18 (HP1125 of H. pylori is a powerful antigen that can induce significant interferon-γ (IFN-γ levels. Previous studies have suggested that IFN-γ plays an important role in H. pylori clearance. However, H. pylori has multiple mechanisms to avoid host immune surveillance for persistent colonization. We generated an omp18 mutant (H. pylori 26695 and H. pylori SS1 strain to examine whether Omp18 interacts with IFN-γ and is involved in H. pylori colonization. qRT-PCR revealed that IFN-γ induced Omp18 expression. qRT-PCR and western blot analysis revealed reduced expressions of virulence factors CagA and NapA in H. pylori 26695 with IFN-γ treatment, but they were induced in the Δomp18 strain. In C57BL/6 mice infected with H. pylori SS1 and the Δomp18 strain, the Δomp18 strain conferred defective colonization and activated a stronger inflammatory response. Signal transducer phosphorylation and transcription 1 (STAT1 activator was downregulated by the wild-type strain but not the Δomp18 strain in IFN-γ-treated macrophages. Furthermore, Δomp18 strain survival rates were poor in macrophages compared to the wild-type strain. We concluded that H. pylori Omp18 has an important function influencing IFN-γ-mediated immune response to participate in persistent colonization.

  2. DRUG RESISTANCE IN HELICOBACTER PYLORI

    Directory of Open Access Journals (Sweden)

    Júlia Silveira VIANNA

    Full Text Available ABSTRACT Background Helicobacter pylori has a worldwide distribution and is associated with the pathogenesis of various diseases of the digestive system. Treatment to eradicate this microorganism involves the use of a combination of antimicrobials, such as amoxicillin, metronidazole, clarithromycin, and levofloxacin, combined with proton pump inhibitors. Although the current therapy is effective, a high rate of treatment failure has been observed, mainly because of the acquisition of point mutations, one of the major resistance mechanisms developed by H. pylori. This phenomenon is related to frequent and/or inappropriate use of antibiotics. Conclusion This review reported an overview of the resistance to the main drugs used in the treatment of H. pylori, confirming the hypothesis that antibacterial resistance is a highly local phenomenon and genetic characteristics of a given population can influence which therapy is the most appropriate.

  3. Diagnosis of Helicobacter pylori Infection.

    Science.gov (United States)

    Tongtawee, Taweesak; Kaewpitoon, Soraya; Kaewpitoon, Natthawut; Dechsukhum, Chavaboon; Leeanansaksiri, Wilairat; Loyd, Ryan A; Matrakool, Likit; Panpimanmas, Sukij

    2016-01-01

    Helicobacter pylori infection plays an important role in the pathogenesis of chronic gastritis, peptic ulcer disease and gastric malignancy. A diagnosis of infection is thus an important part of a treatment strategy of many gastrointestinal tract diseases. Many diagnostic tests are available but all have some limitations in different clinical situations and laboratory settings. A single gold standard cannot available, but be used for diagnosis of Helicobacter pylori infection in daily clinical practice in all areas, so several techniques have been developed to give reliable results, especially focusing on real time endoscopic features. The narrow band imaging system (NBI) and high resolution endoscopy are imaging techniques for enhanced visualization of infected mucosa and premalignant gastric lesions. The aim of this article is to review the current diagnostic options and possible future developments detection of Helicobacter pylori infection.

  4. Lactobacillus plantarum B7 inhibits Helicobacter pylori growth and attenuates gastric inflammation

    Institute of Scientific and Technical Information of China (English)

    Chompoonut Sunanliganon; Duangporn Thong-Ngam; Somying Tumwasorn; Naruemon Klaikeaw

    2012-01-01

    AIM:To determine the anti-Helicobacter property of Lactobacillus plantarum B7 (L.plantarum) B7 supernatants in vitro and the protective effects of L.plantarum B7 on serum tumor necrosis factor-alpha (TNF-α),gastric malondialdehyde (MDA) level,apoptosis,and histopathology in Helicobacter pylori (H.pylorl)-induced gastric inflammation in rats.METHODS:In vitro,the inhibition of H,pylori growth was examined using L.plantarum B7 supernatants at pH 4 and pH 7 and at the concentration of 1×,5× and 10× on plates inoculated with H.pylori.The inhibitory effect of H.pylori was interpreted by the size of the inhibition zone.In vitro,male Sprague-Dawley rats were randomly divided into four groups including group 1 (control group),group 2 (H.pylori infected group),group 3 (H.pylori infected with L.plantarum B7 10é CFUs/mL treated group) and group 4 (H.pylori infected with L.plantarum B7 1010 CFUs/mL treated group).One week after H.pylori inoculation,L.plantarum B7 106 CFUs/mL or 1010 CFUs/mL were fed once daily to group 3 and group 4,respectively,for one week.Blood and gastric samples were collected at the end of the study.RESULTS:In vitro,at intact pH 4,mean inhibitory zone diameters of 8.5 mm and 13 mm were noted at concentrations of 5× and 10× of L.plantarum B7supernatant disks,respectively.At adjusted pH 7,L.plantarum B7 supernatants at concentrations of 5 × and 10× yielded mean inhibitory zone diameters of 6.5 mm and 11 mm,respectively.In the in vitro study,in group 2,stomach histopathology revealed mild to moderate H.pylori colonization and inflammation.The level of gastric MDA and epithelial cell apoptosis were significantly increased compared with group 1.The serum TNF-α level was significant decreased in group 3compared with group 2 (P < 0.05).In addition,L.plantarum B7 treatments resulted in a significant improvement in stomach pathology,and decreased gastric MDA level and apoptotic epithelial cells.CONCLUSION:L.plantarum B7 supernatant inhibits H.pylori

  5. Novel epidermal growth factor receptor pathway mediates release of human β-defensin 3 from Helicobacter pylori-infected gastric epithelial cells.

    Science.gov (United States)

    Muhammad, Jibran S; Zaidi, Syed F; Zhou, Yue; Sakurai, Hiroaki; Sugiyama, Toshiro

    2016-04-01

    Persistent Helicobacter pylori (H. pylori) infection in hostile gastric mucosa can result in gastric diseases. Helicobacter pylori induces to express antimicrobial peptides from gastric epithelial cells, especially human β-defensin 3 (hBD3), as an innate immune response, and this expression of hBD3 is mediated by epidermal growth factor receptor (EGFR) activation. In this study, we found that phosphorylation of a serine residue of EGFR via transforming growth factor β-activated kinase-1 (TAK1), and subsequent p38α activation is essential for H. pylori-induced hBD3 release from gastric epithelial cells. We showed that this pathway was dependent on H. pylori type IV secretion system and was independent of H. pylori-derived CagA or peptidoglycan. H. pylori infection induced phosphorylation of serine residue of EGFR, and this phosphorylation was followed by internalization of EGFR; consequently, hBD3 was released at an early phase of the infection. In the presence of TAK1 or p38α inhibitors, synthesis of hBD3 was completely inhibited. Similar results were observed in EGFR-, TAK1- or p38α-knockdown cells. However, NOD1 knockdown in gastric epithelial cells did not inhibit hBD3 induction. Our study has firstly demonstrated that this novel EGFR activating pathway functioned to induce hBD3 at an early phase of H. pylori infection.

  6. Combining anti-miR-155 with chemotherapy for the treatment of lung cancers.

    Science.gov (United States)

    Van Roosbroeck, Katrien; Fanini, Francesca; Setoyama, Tetsuro; Ivan, Cristina; Rodriguez-Aguayo, Cristian; Fuentes-Mattei, Enrique; Xiao, Lianchun; Vannini, Ivan; Redis, Roxana; D'Abundo, Lucilla; Zhang, Xinna; Nicoloso, Milena S; Rossi, Simona; Gonzalez-Villasana, Vianey; Rupaimoole, Rajesha; Ferracin, Manuela; Morabito, Fortunato; Neri, Antonino; Ruvolo, Peter; Ruvolo, Vivian R; Pecot, Chad V; Amadori, Dino; Aruzzo, Lynne; Calin, Steliana; Wang, Xuemei; You, M James; Ferrajoli, Alessandra; Orlowski, Robert Z; Plunkett, William; Lichtenberg, Tara; Davuluri, Ramana V; Berindan-Neagoe, Ioana; Negrini, Massimo; Wistuba, Ignacio I; Hagop, Kantarjian; Sood, Anil K; Lopez-Berestein, Gabriel; Keating, Michael J; Fabbri, Muller; Calin, George A

    2016-11-30

    Purpose The oncogenic miR-155 is upregulated in many human cancers and its expression is increased in more aggressive and therapy resistant tumors, but the molecular mechanisms underlying miR-155-induced therapy resistance are not fully understood. The main objectives of this study were to determine the role of miR-155 in resistance to chemotherapy and to evaluate anti-miR-155 treatment to chemosensitize tumors. Experimental Design We performed in vitro studies on cell lines to investigate the role of miR-155 in therapy resistance. To assess the effects of miR-155 inhibition on chemoresistance, we used an in vivo orthotopic lung cancer model of athymic nude mice, which we treated with anti-miR-155 alone or in combination with chemotherapy. To analyze the association of miR-155 expression and the combination of miR-155 and TP53 expression with cancer survival, we studied 956 patients with lung cancer, chronic lymphocytic leukemia and acute lymphoblastic leukemia. Results We demonstrate that miR-155 induces resistance to multiple chemotherapeutic agents in vitro, and that downregulation of miR-155 successfully resensitizes tumors to chemotherapy in vivo. We show that anti-miR-155-DOPC can be considered non-toxic in vivo. We further demonstrate that miR-155 and TP53 are linked in a negative feedback mechanism, and demonstrate that a combination of high expression of miR-155 and low expression of TP53 is significantly associated with shorter survival in lung cancer. Conclusions Our findings support the existence of a miR-155/TP53 feedback loop, which is involved in resistance to chemotherapy and which can be specifically targeted to overcome drug resistance, an important cause of cancer-related death.

  7. Loss of MicroRNA-155 protects the heart from pathological cardiac hypertrophy.

    Science.gov (United States)

    Seok, Hee Young; Chen, Jinghai; Kataoka, Masaharu; Huang, Zhan-Peng; Ding, Jian; Yan, Jinglu; Hu, Xiaoyun; Wang, Da-Zhi

    2014-05-09

    In response to mechanical and pathological stress, adult mammalian hearts often undergo mal-remodeling, a process commonly characterized as pathological hypertrophy, which is associated with upregulation of fetal genes, increased fibrosis, and reduction of cardiac dysfunction. The molecular pathways that regulate this process are not fully understood. To explore the function of microRNA-155 (miR-155) in cardiac hypertrophy and remodeling. Our previous work identified miR-155 as a critical microRNA that repressed the expression and function of the myocyte enhancer factor 2A. In this study, we found that miR-155 is expressed in cardiomyocytes and that its expression is reduced in pressure overload-induced hypertrophic hearts. In mouse models of cardiac hypertrophy, miR-155 null hearts suppressed cardiac hypertrophy and cardiac remodeling in response to 2 independent pathological stressors, transverse aortic restriction and an activated calcineurin transgene. Most importantly, loss of miR-155 prevents the progress of heart failure and substantially extends the survival of calcineurin transgenic mice. The function of miR-155 in hypertrophy is confirmed in isolated cardiomyocytes. We identified jumonji, AT rich interactive domain 2 (Jarid2) as an miR-155 target in the heart. miR-155 directly represses Jarid2, whose expression is increased in miR-155 null hearts. Inhibition of endogenous Jarid2 partially rescues the effect of miR-155 loss in isolated cardiomyocytes. Our studies uncover miR-155 as an inducer of pathological cardiomyocyte hypertrophy and suggest that inhibition of endogenous miR-155 might have clinical potential to suppress cardiac hypertrophy and heart failure.

  8. Protein interaction network related to Helicobacter pylori infection response

    Institute of Scientific and Technical Information of China (English)

    Kyu Kwang Kim; Han Bok Kim

    2009-01-01

    AIM: To understand the complex reaction of gastric inflammation induced by Helicobacter pylori (H pylori ) in a systematic manner using a protein interaction network. METHODS: The expression of genes significantly changed on microarray during H pylori infection was scanned from the web literary database and translated into proteins. A network of protein interactions was constructed by searching the primary interactions of selected proteins. The constructed network was mathematically analyzed and its biological function was examined. In addition, the nodes on the network were checked to determine if they had any further functional importance or relation to other proteins by extending them.RESULTS: The scale-free network showing the relationship between inflammation and carcinogenesis was constructed. Mathematical analysis showed hub and bottleneck proteins, and these proteins were mostly related to immune response. The network contained pathways and proteins related to H pylori infection, such as the JAK-STAT pathway triggered by interleukins. Activation of nuclear factor (NF)-kB, TLR4, and other proteins known to function as core proteins of immune response were also found.These immune-related proteins interacted on the network with pathways and proteins related to the cell cycle, cell maintenance and proliferation, and transcription regulators such as BRCA1, FOS, REL, and zinc finger proteins. The extension of nodes showed interactions of the immune proteins with cancerrelated proteins. One extended network, the core network, a summarized form of the extended network, and cell pathway model were constructed. CONCLUSION: Immune-related proteins activated by H pylori infection interact with proto-oncogene proteins. The hub and bottleneck proteins are potential drug targets for gastric inflammation and cancer.

  9. Helicobacter pylori infection and gastric cancer%幽门螺杆菌感染与胃癌

    Institute of Scientific and Technical Information of China (English)

    时昭红; 刘浩

    2011-01-01

    2005年的诺贝尔生理学和医学奖授予了幽门螺杆菌(Helicobacter pylori,H.pylori)的发现人巴里·马歇尔和罗宾·沃伦教授.迄今有大量的流行病学、临床和实验研究支持H.pylori是胃癌的致病因素,但其具体致病机制尚不完全明了.本文就H.pylori感染和胃癌的流行病学研究,H.pylori感染致胃癌的动物实验模型研究,H.pylori毒力基因与胃癌的关系,H.pylori感染与胃癌相关基因的关系和H.pylori感染与胃上皮细胞增殖和凋亡的关系等方面,系统阐述H.pylori感染和胃癌之间的关系.%The 2005 Nobel Prize in Physiology and Medicine was awarded to Barry Marshall and Robin Warren for their discovery of Helicobacter pylori (H. Pylori). Now numerous epidemiological, clinical and experimental studies and reports emphasized the crucial role of H. Pylori in the pathogenesis of gastric cancer (GC), but the specific mechanism is still unknown. In this paper, we undertake a systematic review of H. Pylori infection-related GC epidemiological studies, animal models of H. Pylori infection-induced GC, the relationship between the virulence genes of H. Pylori and GC, the links between H. Pylori infection and genes related to GC, and the correlation of H. Pylori infection with gastric epithelial proliferation and apoptosis.

  10. Helicobacter pylori lipopolysaccharide is synthesized via a novel pathway with an evolutionary connection to protein N-glycosylation.

    Directory of Open Access Journals (Sweden)

    Isabelle Hug

    2010-03-01

    Full Text Available Lipopolysaccharide (LPS is a major component on the surface of Gram negative bacteria and is composed of lipid A-core and the O antigen polysaccharide. O polysaccharides of the gastric pathogen Helicobacter pylori contain Lewis antigens, mimicking glycan structures produced by human cells. The interaction of Lewis antigens with human dendritic cells induces a modulation of the immune response, contributing to the H. pylori virulence. The amount and position of Lewis antigens in the LPS varies among H. pylori isolates, indicating an adaptation to the host. In contrast to most bacteria, the genes for H. pylori O antigen biosynthesis are spread throughout the chromosome, which likely contributed to the fact that the LPS assembly pathway remained uncharacterized. In this study, two enzymes typically involved in LPS biosynthesis were found encoded in the H. pylori genome; the initiating glycosyltransferase WecA, and the O antigen ligase WaaL. Fluorescence microscopy and analysis of LPS from H. pylori mutants revealed that WecA and WaaL are involved in LPS production. Activity of WecA was additionally demonstrated with complementation experiments in Escherichia coli. WaaL ligase activity was shown in vitro. Analysis of the H. pylori genome failed to detect a flippase typically involved in O antigen synthesis. Instead, we identified a homolog of a flippase involved in protein N-glycosylation in other bacteria, although this pathway is not present in H. pylori. This flippase named Wzk was essential for O antigen display in H. pylori and was able to transport various glycans in E. coli. Whereas the O antigen mutants showed normal swimming motility and injection of the toxin CagA into host cells, the uptake of DNA seemed to be affected. We conclude that H. pylori uses a novel LPS biosynthetic pathway, evolutionarily connected to bacterial protein N-glycosylation.

  11. Dispepsia ed Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Giovanni Fornaciari

    2003-09-01

    Full Text Available The effect of Helicobacter pylori (HP eradication on functional dyspepsia has been analysed in several clinical trials, including large, controlled and well-designed studies as well as small, flowed studies. The results of these studies indicate that HP infection does not play a major role in the aetiology of this disease and that HP eradication improves dyspeptic symptoms in no more than 15% of patients as compared to placebo. From a practical point of view 15 patients need to be treated for one to benefit while, in duodenal ulcer, 1.4 patient need to be treated for one to benefit. It remains to be elucidated if HP eradication in functional dyspepsia is useful to reduce the risk of developing organic dyspepsia (namely peptic ulcer in functional dyspepsia. In uninvestigated dyspepsia the management of HP infection in primary care has been fully debated.Two therapeutics strategies have been proposed: test and scope and test and treat. The value of test and treat strategy over alternative strategies has been demonstrated in several decision analyses. HP test and scope increases costs in primary care without improving symptoms and saves only 15% of endoscopies.

  12. Helicobacter pylori Is Associated with miR-133a Expression through Promoter Methylation in Gastric Carcinogenesis.

    Science.gov (United States)

    Lim, Joo Hyun; Kim, Sang Gyun; Choi, Ji Min; Yang, Hyo-Joon; Kim, Joo Sung; Jung, Hyun Chae

    2017-09-28

    To investigate whether Helicobacter pylori eradication can reverse epigenetic silencing of microRNAs (miRNAs) which are associated with H. pylori-induced gastric carcinogenesis. We examined expression and promoter methylation of miR-34b/c, miR-133a, let-7a, and let-7i in gastric cancer cell line, before/after demethylation. Among them, epigenetically controlled miRNAs were identified. Their expression and promoter methylation was examined in human tissues of H. pylori-positive gastric cancer (T), H. pylori-positive gastritis (H), and H. pylori-negative controls (C). We also compared changes of miRNA expression and promoter methylation in H. pylori-positive patients who were endoscopically treated for early gastric cancer, between baseline and 1 year later according to eradication status. In gastric cancer cell line, miR-34b/c, and miR-133a showed epigenetic silencing. In human tissues, miR-34b/c and miR-133a showed serial increase of promoter methylation in order of C, H, and T (all, p〈0.01), and the miR-133a expression showed serial decrease (C vs H, p=0.02; H vs T, p=0.01; C vs T, p〈0.01) while miR-34b and miR-34c expressions did not. H. pylori eradication induced decrease of methylation (p〈0.01) and increase of miR-133a expression (p=0.03), compared with noneradication group. This result suggests H. pylori eradication could reverse methylation-silencing of miR-133a which is involved in H. pylori-induced gastric carcinogenesis.

  13. An analysis of the curative effect of saccharomyces boulardii combined with a standard triple therapy in the treatment of 55 cases of helicobacter pylori-induced peptic ulcer%布拉酵母菌联合标准三联疗法治疗幽门螺杆菌消化性溃疡55例效果分析

    Institute of Scientific and Technical Information of China (English)

    朱路平; 肖飞

    2014-01-01

    目的:分析布拉酵母菌联合标准三联疗法治疗幽门螺杆菌消化性溃疡的临床疗效和安全性。方法随机将109例确诊幽门螺杆菌消化性溃疡进行分组,对照组54例予标准三联疗法治疗,实验组55例予布拉氏酵母菌联合标准三联疗法治疗,观察两组溃疡愈合效果、幽门螺杆菌清除率和不良反应情况。结果实验组溃疡愈合总有效率92.73%明显高于对照组79.63%(P0.05)。结论布拉氏酵母菌联合标准三联疗法能够通过快速恢复幽门螺杆菌消化性溃疡患者肠道菌群的动态平衡、抑制幽门螺杆菌在胃黏膜上皮定值和成长等作用提高幽门螺杆菌清除率。%Objective To analyze the clinical effect and safety of saccharomyces boulardii combined with a standard triple therapy in the treatment of helicobacter pylori-induced peptic ulcer. Methods A total of 109 patients who were diagnosed as helicobacter pylori-induced peptic ulcer were randomly assigned to control group and experimental group. The control group of 54 patients received a standard triple therapy, and the experimental group of 55 patients received saccharomyces boulardii combined with a standard triple therapy. Ulcer recovery, clearance rate of helicobacter pylori and adverse events were observed between the two groups. Results The total effective rate of ulcer recovery in the ex-perimental group was 92.73%, significantly higher than that of 79.63%in the control group(P<0.05); The clearance rate of helicobacter pylori in the experimental group was 90.91%, significantly higher than that of 75.93% in the control group (P<0.05); The incidence of adverse events in the experimental group was 12.73%, and P value was over 0.05 compared to that of 11.11% in the control group. Conclusion The saccharomyces boulardii combined with a standard triple therapy in the treatment of helicobacter pylori-induced peptic ulcer has a significantly effect, and is able to en-hance the

  14. Standardization and in-house ELISA setup for helicobacter pylori serologic diagnosis

    Directory of Open Access Journals (Sweden)

    Shahrestani T

    2001-09-01

    Full Text Available Helicobacter pylori (H.pylori is the most prominent causative agent of gastroduodenal diseases all over the world. Other manifestations such as urticaria and coronary heart diseases, also are suspected to be induced by H.pylori. Non invasive methods are preferred for diagnosis; and ELISA, because of its reliability, speed, sensitivity and specificity is widely preferred as diagnostic tool. Previously we have used IFA, and here, we report an indirect ELISA technique for H.pylori diagnosis. First, 9 strains, of H.pylori isolated from biopsies, were cultured, and the soluble crude antigen was used to coat ELISA plates. Antigen concentration and conjugated antiserum dilution were optimised using checker board method. In this study the gold standard was: rapid urease test, culture and direct smear. Patient serum dillution and the cut-off value was determind, using 22 negative and 30 positive confirmed samples according to ROC curve and the results were compared with a commercial kit. The sensitivity and specificity of this method were 93.2 percent and 95.4 percent respectively. A commercial ELISA Kit, was used and compared simultaneously. The sensitivity and specificity were 87.8 percent and 73 percent respectively. Therefore, regarding the acceptable sensitivity and specificity, ease of work of ELISA, being economical and non-invasive, it can be employed in diagnosis of H.pylori infection and also in epidemiological studies.

  15. Helicobacter pylori infection and inflammatory bowel disease: Is there a link?

    Science.gov (United States)

    Papamichael, Konstantinos; Konstantopoulos, Panagiotis; Mantzaris, Gerassimos J

    2014-01-01

    Helicobacter pylori (H. pylori) infection is one of the most widely spread infectious diseases in humans. It can cause chronic gastritis, peptic ulcer disease and gastric malignancies and has been associated with extra-gastric disorders. H. pylori elicit a chronic systemic inflammatory response which, under certain conditions, may trigger autoimmune reactions and may be implicated in the pathogenesis of autoimmune diseases. Although the pathogenesis of inflammatory bowel disease (IBD) is unknown, it is thought to result from complex interactions between environmental factors and microbiota in the gut of individuals who are genetically susceptible. Several bacterial and viral agents have been implicated in the aetiology of IBD. In theory, H. pylori infection could be involved in the pathogenesis of IBD by inducing alterations in gastric and/or intestinal permeability or by causing immunological derangements resulting in absorption of antigenic material and autoimmunity via various immunological pathways. Similar mechanisms may also be responsible for the co-existence of IBD with other autoimmune diseases and/or extra-intestinal manifestations. However, the epidemiological data fail to support this association. In fact, various studies indicate that the prevalence of H. pylori infection is low in patients with IBD, suggesting a protective role for this infection in the development of IBD. In this report, we aim to shed light on proposed mechanisms and confounding factors underlying the potential link between H. pylori infection and IBD. PMID:24914359

  16. The impact of Helicobacter pylori infection on the gastric microbiota of the rhesus macaque.

    Directory of Open Access Journals (Sweden)

    Miriam E Martin

    Full Text Available Helicobacter pylori colonization is highly prevalent among humans and causes significant gastric disease in a subset of those infected. When present, this bacterium dominates the gastric microbiota of humans and induces antimicrobial responses in the host. Since the microbial context of H. pylori colonization influences the disease outcome in a mouse model, we sought to assess the impact of H. pylori challenge upon the pre-existing gastric microbial community members in the rhesus macaque model. Deep sequencing of the bacterial 16S rRNA gene identified a community profile of 221 phylotypes that was distinct from that of the rhesus macaque distal gut and mouth, although there were taxa in common. High proportions of both H. pylori and H. suis were observed in the post-challenge libraries, but at a given time, only one Helicobacter species was dominant. However, the relative abundance of non-Helicobacter taxa was not significantly different before and after challenge with H. pylori. These results suggest that while different gastric species may show competitive exclusion in the gastric niche, the rhesus gastric microbial community is largely stable despite immune and physiological changes due to H. pylori infection.

  17. Helicobacter pylori Infection and Dietary Factors Act Synergistically to Promote Gastric Cancer.

    Science.gov (United States)

    Raei, Negin; Behrouz, Bahador; Zahri, Saber; Latifi-Navid, Saeid

    2016-01-01

    However, the incidence of gastric cancer (GC) has been decreased in past decades; GC is the second cause of cancer related death in the world. Evidence has illustrated that several factors including Helicobacter pylori (H. pylori) infection, host genetics, and environmental factors (smoking and particularly diet) may play a crucial role in gastric carcinogenesis. It has been demonstrated that high consumption of fresh fruits, vegetables, high level of selenium and zinc in drinking water, sufficient iron, and cholesterol protect against GC, while; smoked , pickled, and preserved foods in salt, and nitrites increase the risk of GC. Epidemiological studies have also proved that H. pylori infection and a high salt diet could independently induce atrophic gastritis and intestinal metaplasia. Recently, studies have been demonstrated that dietary factors directly influence H. pylori virulence. The use of appropriate diet could reduce levels of H. pylori colonization or virulence and prevent or delay development of peptic ulcers or gastric carcinoma. This is attractive from a number of perspectives including those of cost, treatment tolerability, and cultural acceptability. This review will describe new insights into the pathogenesis of H. pylori in relation to environmental factors, especially dietary, not only to find the developed means for preventing and treating GC, but also for understanding the role of chronic inflammation in the development of other malignancies.

  18. Toll-like receptor 2: An important immunomodulatory molecule during Helicobacter pylori infection.

    Science.gov (United States)

    Nemati, Maryam; Larussa, Tiziana; Khorramdelazad, Hossein; Mahmoodi, Merat; Jafarzadeh, Abdollah

    2017-06-01

    Toll like receptors (TLRs) are an essential subset of pathogen recognition receptors (PRRs) which identify the microbial components and contribute in the regulation of innate and adaptive immune responses against the infectious agents. The TLRs, especially TLR2, TLR4, TLR5 and TLR9, participate in the induction of immune response against H. pylori. TLR2 is expressed on a number of immune and non-immune cells and recognizes a vast broad of microbial components due to its potential to form heterodimers with other TLRs, including TLR1, TLR6 and TLR10. A number of H. pylori-related molecules may contribute to TLR2-dependent responses, including HP-LPS, HP-HSP60 and HP-NAP. TLR2 plays a pivotal role in regulation of immune response to H. pylori through activation of NF-κB and induction of cytokine expression in epithelial cells, monocytes/macrophages, dendritic cells, neutrophils and B cells. The TLR2-related immune response that is induced by H. pylori-derived components may play an important role regarding the outcome of the infection toward bacterial elimination, persistence or pathological reactions. The immunomodulatory and immunoregulatory roles of TLR2 during H. pylori infection were considered in this review. TLR2 could be considered as an interesting therapeutic target for treatment of H. pylori-related diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Refractory iron deficiency anemia and Helicobacter Pylori Infection in pediatrics: A review

    Science.gov (United States)

    Gheibi, Sh; Farrokh-Eslamlou, HR; Noroozi, M; Pakniyat, A

    2015-01-01

    Background Since the discovery of Helicobacter pylori, several clinical reports have demonstrated that H. Pylori infection has emerged as a new cause of refractory iron stores in children. We carried out a systematic literature review to primarily evaluate the existing evidence on the association between childhood H. Pylori infection and iron deficiency anemia (IDA) and secondly, to investigate the beneficial effects of bacterium elimination. Material and Methods This review concerns important pediatric studies published from January 1991 to October 2014. Fourteen case reports and series of cases, 24 observational epidemiologic studies, seven uncontrolled trials, and 16 randomized clinical trials were included in the review. Results Although there are a few observational epidemiologic studies and some randomized trials mostly due to the potential confounders, most studies reported a positive association linking between H. Pylori infection and iron deficiency or iron deficiency anemia among children. In addition, it seems that elimination of H. Pylori infection induces beneficial effects on iron deficiency. Conclusions Since the evidence for the association of H. pylori eradication therapy and refractory childhood IDA is not enough and there are contrasting data about such association, future high quality and cohort researches are needed to determine the causal association. PMID:25914802

  20. Mixed Infections of Helicobacter pylori Isolated from Patients with Gastrointestinal Diseases in Taiwan

    Directory of Open Access Journals (Sweden)

    Chih-Ho Lai

    2016-01-01

    Full Text Available Background. Persistent Helicobacter pylori infection may induce several upper gastrointestinal diseases. Two major virulence factors of H. pylori, vacuolating cytotoxin A (VacA and cytotoxin-associated gene A (CagA, are thought to be associated with the severity of disease progression. The distribution of vacA and cag-pathogenicity island (cag-PAI alleles varies in H. pylori isolated from patients in different geographic regions. Aim. To assess the association between mixed infection of H. pylori clinical isolates from Taiwanese patients and the severity of gastrointestinal diseases. Methods. A total of 70 patients were enrolled in this study. Six distinct and well-separated colonies were isolated from each patient and 420 colonies were analyzed to determine the genotypes of virulence genes. Results. The prevalence of mixed infections of all H. pylori-infected patients was 28.6% (20/70. The rate of mixed infections in patients with duodenal ulcer (47.6% was much higher than that with other gastrointestinal diseases (P<0.05. Conclusions. H. pylori mixed infections show high genetic diversity that may enhance bacterial adaptation to the hostile environment of the stomach and contribute to disease development.

  1. Mixed Infections of Helicobacter pylori Isolated from Patients with Gastrointestinal Diseases in Taiwan

    Science.gov (United States)

    Huang, Ju-Chun; Chiang-Ni, Chuan; Li, Ju-Pi; Wu, Lii-Tzu; Wu, Hua-Shan; Sun, Yu-Chen; Lin, Mei-Ling; Lee, Ju-Fang

    2016-01-01

    Background. Persistent Helicobacter pylori infection may induce several upper gastrointestinal diseases. Two major virulence factors of H. pylori, vacuolating cytotoxin A (VacA) and cytotoxin-associated gene A (CagA), are thought to be associated with the severity of disease progression. The distribution of vacA and cag-pathogenicity island (cag-PAI) alleles varies in H. pylori isolated from patients in different geographic regions. Aim. To assess the association between mixed infection of H. pylori clinical isolates from Taiwanese patients and the severity of gastrointestinal diseases. Methods. A total of 70 patients were enrolled in this study. Six distinct and well-separated colonies were isolated from each patient and 420 colonies were analyzed to determine the genotypes of virulence genes. Results. The prevalence of mixed infections of all H. pylori-infected patients was 28.6% (20/70). The rate of mixed infections in patients with duodenal ulcer (47.6%) was much higher than that with other gastrointestinal diseases (P < 0.05). Conclusions. H. pylori mixed infections show high genetic diversity that may enhance bacterial adaptation to the hostile environment of the stomach and contribute to disease development. PMID:27738429

  2. Onset of Ulcerative Colitis after Helicobacter pylori Eradication Therapy: A Case Report.

    Science.gov (United States)

    Chiba, Mitsuro; Tsuji, Tsuyotoshi; Takahashi, Kenichi; Komatsu, Masafumi; Sugawara, Takeshi; Ono, Iwao

    2016-01-01

    In Japan, Helicobacter pylori eradication has been approved since 2013 for treatment of H pylori-induced chronic gastritis, in an attempt to reduce the prevalence of gastric cancer, a leading cancer in Japan. H pylori infection affects more than 50% of the world's population. H pylori eradication therapy is generally safe. To our knowledge, no case of newly diagnosed ulcerative colitis occurring immediately after H pylori eradication therapy has previously been reported.A 63-year-old man received a diagnosis of chronic gastritis and H pylori infection. In early March 2014, primary H pylori eradication therapy was initiated; lansoprazole, amoxicillin, and clarithromycin were administered for 1 week. Beginning on the fourth day, he had watery diarrhea twice a day. From the 11th day, bloody stools and watery diarrhea increased to 6 times a day. Colonoscopy, performed on the 40th day after termination of drug therapy, revealed diffuse inflammation in the distal aspect of the colon, with histologic findings consistent with ulcerative colitis. He was admitted to the hospital and was provided with a semivegetarian diet and metronidazole. He noticed a gradual decrease in the amount of blood in his feces then a disappearance of the blood. A fecal occult blood test on the 11th hospital day recorded 337 ng/mL. Fecal occult blood test is not indicated during macroscopic bloody stool but is indicated after disappearance of bloody stool. Therefore, he achieved clinical remission by the 11th hospital day. He was in remission on discharge.New onset of ulcerative colitis should be added to a list of adverse events of H pylori eradication therapy.

  3. Coinfection with Helicobacter pylori and Opisthorchis viverrini Enhances the Severity of Hepatobiliary Abnormalities in Hamsters.

    Science.gov (United States)

    Dangtakot, Rungtiwa; Pinlaor, Somchai; Itthitaetrakool, Upsornsawan; Chaidee, Apisit; Chomvarin, Chariya; Sangka, Arunnee; Wilailuckana, Chotechana; Pinlaor, Porntip

    2017-04-01

    Persistent infection with Opisthorchis viverrini causes hepatobiliary abnormalities, predisposing infected individuals to cholangiocarcinoma (CCA). In addition, Helicobacter pylori is highly prevalent in most countries and is a possible risk factor for CCA; however, its role in enhancing hepatobiliary abnormality is unclear. Here, we investigated the effects of coinfection with H. pylori and O. viverrini on hepatobiliary abnormality. Hamsters were divided into four groups: (i) normal, (ii) H. pylori infected (HP), (iii) O. viverrini infected (OV), and (iv) O. viverrini and H. pylori infected (OV+HP). At 6 months postinfection, PCR and immunohistochemistry were used to test for the presence of H. pylori in the stomach, gallbladder, and liver. In the liver, H. pylori was detected in the following order: OV+HP, 5 of 8 (62.5%); HP, 2 of 5 (40%); OV, 2 of 8 (25%). H. pylori was not detected in normal (control) liver tissues. Coinfection induced the most severe hepatobiliary abnormalities, including periductal fibrosis, cholangitis, and bile duct hyperplasia, leading to a significantly decreased survival rate of experimental animals. The greatest thickness of periductal fibrosis was associated with a significant increase in fibrogenesis markers (expression of alpha smooth muscle actin and transforming growth factor beta). Quantitative reverse transcription-PCR revealed that the highest expression levels of genes for proinflammatory cytokines (interleukin-1 [IL-1], IL-6, and tumor necrosis factor alpha) were also observed in the OV+HP group. These results suggest that coinfection with H. pylori and O. viverrini increased the severity of hepatobiliary abnormalities to a greater extent than either single infection did.

  4. Helicobacter pylori Eradication in Patients with Immune Thrombocytopenic Purpura: A Review and the Role of Biogeography.

    Science.gov (United States)

    Frydman, Galit H; Davis, Nick; Beck, Paul L; Fox, James G

    2015-08-01

    Idiopathic thrombocytopenic purpura (ITP) is typically a diagnosis of exclusion, assigned by clinicians after ruling out other identifiable etiologies. Since a report by Gasbarrini et al. in 1998, an accumulating body of evidence has proposed a pathophysiological link between ITP and chronic Helicobacter pylori (H. pylori) infection. Clinical reports have described a spontaneous resolution of ITP symptoms in about 50% of chronic ITP patients following empirical treatment of H. pylori infection, but response appears to be geography dependent. Studies have also documented that ITP patients in East Asian countries are more likely to express positive antibody titers against H. pylori-specific cytotoxic-associated gene A (CagA), a virulence factor that is associated with an increased risk for gastric diseases including carcinoma. While a definitive mechanism by which H. pylori may induce thrombocytopenia remains elusive, proposed pathways include molecular mimicry of CagA by host autoantibodies against platelet surface glycoproteins, as well as perturbations in the phagocytic activity of monocytes. Traditional treatments of ITP have been largely empirical, involving the use of immunosuppressive agents and immunoglobulin therapy. However, based on the findings of clinical reports emerging over the past 20 years, health organizations around the world increasingly suggest the detection and eradication of H. pylori as a treatment for ITP. Elucidating the exact molecular mechanisms of platelet activation in H. pylori-positive ITP patients, while considering biogeographical differences in response rates, could offer insight into how best to use clinical H. pylori eradication to treat ITP, but will require well-designed studies to confirm the suggested causative relationship between bacterial infection and an autoimmune disease state. © 2015 John Wiley & Sons Ltd.

  5. The influence of mucus microstructure and rheology in H. pylori infection

    Directory of Open Access Journals (Sweden)

    Rama eBansil

    2013-10-01

    Full Text Available The bacterium Helicobacter pylori (H. pylori, has evolved to survive in the highly acidic environment of the stomach and colonize on the epithelial surface of the gastric mucosa. Its pathogenic effects are well known to cause gastritis, peptic ulcers and gastric cancer. In order to infect the stomach and establish colonies on the mucus epithelial surface, the bacterium has to move across the gel-like gastric mucus lining of the stomach under acidic conditions. In this review we address the question of how the bacterium gets past the protective mucus barrier from a biophysical perspective. We begin by reviewing the molecular structure of gastric mucin and discuss the current state of understanding concerning mucin polymerization and low pH induced gelation. We then focus on the viscoelasticity of mucin in view of its relevance to the transport of particles and bacteria across mucus, the key first step in H. pylori infection. The second part of the review focuses on the motility of H. pylori in mucin solutions and gels, and how infection with H. pylori in turn impacts the viscoelastic properties of mucin. We present recent microscopic results tracking the motion of H. pylori in mucin solutions and gels. We then discuss how the biochemical strategy of urea hydrolysis required for survival in the acid is also relevant to the mechanism that enables flagella driven swimming across the mucus gel layer. Other aspects of the influence of H. pylori infection such as, altering gastric mucin expression, its rate of production and its composition, and the influence of mucin on factors controlling H. pylori virulence and proliferation are briefly discussed with references to relevant literature.

  6. Motility and chemotaxis mediate the preferential colonization of gastric injury sites by Helicobacter pylori.

    Directory of Open Access Journals (Sweden)

    Eitaro Aihara

    2014-07-01

    Full Text Available Helicobacter pylori (H. pylori is a pathogen contributing to peptic inflammation, ulceration, and cancer. A crucial step in the pathogenic sequence is when the bacterium first interacts with gastric tissue, an event that is poorly understood in vivo. We have shown that the luminal space adjacent to gastric epithelial damage is a microenvironment, and we hypothesized that this microenvironment might enhance H. pylori colonization. Inoculation with 106 H. pylori (wild-type Sydney Strain 1, SS1 significantly delayed healing of acetic-acid induced ulcers at Day 1, 7 and 30 post-inoculation, and wild-type SS1 preferentially colonized the ulcerated area compared to uninjured gastric tissue in the same animal at all time points. Gastric resident Lactobacillus spp. did not preferentially colonize ulcerated tissue. To determine whether bacterial motility and chemotaxis are important to ulcer healing and colonization, we analyzed isogenic H. pylori mutants defective in motility (ΔmotB or chemotaxis (ΔcheY. ΔmotB (10(6 failed to colonize ulcerated or healthy stomach tissue. ΔcheY (10(6 colonized both tissues, but without preferential colonization of ulcerated tissue. However, ΔcheY did modestly delay ulcer healing, suggesting that chemotaxis is not required for this process. We used two-photon microscopy to induce microscopic epithelial lesions in vivo, and evaluated accumulation of fluorescently labeled H. pylori at gastric damage sites in the time frame of minutes instead of days. By 5 min after inducing damage, H. pylori SS1 preferentially accumulated at the site of damage and inhibited gastric epithelial restitution. H. pylori ΔcheY modestly accumulated at the gastric surface and inhibited restitution, but did not preferentially accumulate at the injury site. H. pylori ΔmotB neither accumulated at the surface nor inhibited restitution. We conclude that bacterial chemosensing and motility rapidly promote H. pylori colonization of injury sites

  7. Helicobacter pylori virulence factors affecting gastric proton pump expression and acid secretion.

    Science.gov (United States)

    Hammond, Charles E; Beeson, Craig; Suarez, Giovanni; Peek, Richard M; Backert, Steffen; Smolka, Adam J

    2015-08-01

    Acute Helicobacter pylori infection of gastric epithelial cells and human gastric biopsies represses H,K-ATPase α subunit (HKα) gene expression and inhibits acid secretion, causing transient hypochlorhydria and supporting gastric H. pylori colonization. Infection by H. pylori strains deficient in the cag pathogenicity island (cag PAI) genes cagL, cagE, or cagM, which do not transfer CagA into host cells or induce interleukin-8 secretion, does not inhibit HKα expression, nor does a cagA-deficient strain that induces IL-8. To test the hypothesis that virulence factors other than those mediating CagA translocation or IL-8 induction participate in HKα repression by activating NF-κB, AGS cells transfected with HKα promoter-Luc reporter constructs containing an intact or mutated NF-κB binding site were infected with wild-type H. pylori strain 7.13, isogenic mutants lacking cag PAI genes responsible for CagA translocation and/or IL-8 induction (cagA, cagζ, cagε, cagZ, and cagβ), or deficient in genes encoding two peptidoglycan hydrolases (slt and cagγ). H. pylori-induced AGS cell HKα promoter activities, translocated CagA, and IL-8 secretion were measured by luminometry, immunoblotting, and ELISA, respectively. Human gastric biopsy acid secretion was measured by microphysiometry. Taken together, the data showed that HKα repression is independent of IL-8 expression, and that CagA translocation together with H. pylori transglycosylases encoded by slt and cagγ participate in NF-κB-dependent HKα repression and acid inhibition. The findings are significant because H. pylori factors other than CagA and IL-8 secretion are now implicated in transient hypochlorhydria which facilitates gastric colonization and potential triggering of epithelial progression to neoplasia.

  8. Helicobacter pylori and Peptic Ulcers

    Centers for Disease Control (CDC) Podcasts

    2010-08-17

    In this podcast, CDC's Dr. David Swerdlow discusses the relationship between Helicobacter pylori and peptic ulcer disease and trends in hospitalization rates for peptic ulcer disease in the United States between 1998 and 2005.  Created: 8/17/2010 by National Center for Emerging and Zoonotic Infectious Diseases.   Date Released: 8/17/2010.

  9. Gastrin and antral G cells in course of Helicobacter pylori eradication: Six months follow up study

    Institute of Scientific and Technical Information of China (English)

    Aleksandra Sokic-Milutinovic; Vera Todorovic; Tomica Milosavljevic; Marjan Micev; Neda Drndarevic; Olivera Mitrovic

    2005-01-01

    apparatus. However, differences between DU and gastritis group were identified.CONCLUSION: H pylori infection induces antral G cell hyperfunction resulting in increased gastrin synthesis and secretion. After eradication therapy complete morphological and functional recovery is observed in patients with gastritis. In the DU patients some other factors unrelated to the H pylori infection influence antral G cell morphology and function.

  10. Oral immunization with HpaA affords therapeutic protective immunity against H. pylori that is reflected by specific mucosal immune responses.

    Science.gov (United States)

    Nyström, Johanna; Svennerholm, Ann-Mari

    2007-03-30

    In the present study, we evaluated the capacity of Helicobacter pylori adhesin A (HpaA), a H. pylori specific colonization factor, to induce therapeutic protection against H. pylori infection in mice. We found that oral immunization of H. pylori infected mice with HpaA induced protection, i.e. significant reduction in bacterial load in the stomach. This was even more pronounced when a combination of HpaA and urease was used. The protection was strongly related to specific mucosal CD4+ T cell responses with a Th1 profile as well as to mucosal IgA responses locally in the stomach. These findings suggest that HpaA is a promising vaccine candidate antigen for use in a therapeutic vaccine against H. pylori.

  11. Helicobacter pylori and Gastrointestinal Malignancies.

    Science.gov (United States)

    Venerito, Marino; Vasapolli, Riccardo; Rokkas, Theodoros; Malfertheiner, Peter

    2015-09-01

    Helicobacter pylori infection is the principal trigger of gastric carcinogenesis and gastric cancer (GC) and remains the third leading cause of cancer-related death in both sexes worldwide. In a big Japanese study, the risk of developing GC in patients with peptic ulcer disease who received H. pylori eradication therapy and annual endoscopic surveillance for a mean of 9.9 years was significantly lower after successful eradication therapy compared to the group with persistent infection (0.21%/year and 0.45%/year, respectively, p = .049). According to a recent meta-analysis, H. pylori eradication is insufficient in GC risk reduction in subjects with advanced precancerous conditions (i.e., intestinal metaplasia and dysplasia). A microsimulation model suggested screening smokers over the age of 50 in the U.S. for serum pepsinogens. This would allow to detect advanced gastric atrophy with endoscopic follow-up of subjects testing positive as a cost-effective strategy to reduce GC mortality. In a Taiwanese study, the anti-H. pylori IgG-based test-and-treat program had lower incremental cost-effectiveness ratios than that with (13)C-urea breath test in both sexes to prevent GC whereas expected years of life lost for GC were higher and the incremental cost-effectiveness ratios of test-and-treat programs were more cost-effective in young adults (30-69 years old) than in elders (>70 years old). With respect to gastrointestinal malignancies other than GC, a meta-analysis confirmed the inverse association between H. pylori infection and esophageal adenocarcinoma. In a Finnish study, H. pylori seropositivity was associated with an increased risk of biliary tract cancers (multivariate adjusted OR 2.63; 95% CI: 1.08-6.37), another meta-analysis showed a slightly increased rate of pancreatic cancer in patients with CagA-negative strains (OR: 1.30; 95% CI: 1.02-1.65), whereas current data suggest that the association between H. pylori and colorectal neoplasms may be population

  12. H pylori are associated with chronic cholecystitis

    Institute of Scientific and Technical Information of China (English)

    Dong-Feng Chen; Lu Hu; Ping Yi; Wei-Wen Liu; Dian-Chun Fang; Hong Cao

    2007-01-01

    AIM:To study whether H pylori are associated with chronic cholecystitis.METHODS:The subjects were divided into three groups:H pylori-infected cholecystitis group,H pylorinegative cholecystitis group and control group.Pathologic changes of the gallbladder were observed by optic and electronic microscopes and the levels of interleukin-1,6 and 8(IL-1,6 and 8)were detected by radioimmunoassay.RESULTS:Histological evidence of chronic cholecystitis including degeneration,necrosis,inflammatory cell infiltration,were found in the region where H pylori-colonized.Levels of IL-1,6 and 8 in gallbladder mucosa homogenates were significantly higher in H pylori-infected cholecystitis group than those in H pylori-negative cholecystitis group and control group.CONCLUSION:H pylori infection may be related to cholecystitis.

  13. Interaction or relationship between Helicobacter pylori and non-steroidal anti-inflammatory drugs in upper gastrointestinal diseases

    Institute of Scientific and Technical Information of China (English)

    Kai-Yu Ji; Fu-Lian Hu

    2006-01-01

    According to a meta-analysis, H pylori and non-steroidal anti-inflammatory drugs (NSAID) independently and significantly increase the risk of gastroduodenal ulcer and ulcer bleeding. Their coincidence is frequent,demonstration of a possible relationship and consequent attitude is of important implications. But unfortunately,no consensus has been approved in the past years and their interactions are still controversial. H pylori and NSAID are known to share a number of pathogenic mechanisms, but there is no evidence for the significant synergic action between these two risk factors. Their relationship is independent, additive, synergistic or antagonistic without considering the influence of other factors because studies on this subject are different in almost all aspects of their methodology, including the definition of a NSAID user as well as the types,doses, duration and their indications for NSAID use,as well as their end-points, definition of dyspepsia and regimes used for eradication of H pylori. These might contribute to the conflicting results and opinions. H pylori infection in humans does not act synergistically with NSAID on ulcer healing, and there is no need to eradicate it. This notion is supported by the finding that the eradication of H pylori does not affect NSAIDinduced gastropathy treated with omeprazole and that H pylori infection induces a strong cyclooxygenase-2(COX-2) expression resulting in excessive biosynthesis of gastroprotective prostaglandin which in turn counteracts NSAID-induced gastropathy and heals the existing ulcer.Other investigators claimed that H pylori infection acts synergistically with NSAID on ulcer development, and H pylori should be eradicated, particularly at the start of long-term NSAID therapy. Eradication of H pylori prior to NSAID treatment does not appear to accelerate ulcer healing or to prevent recurrent ulcers in NSAID users.However, some recommendations can be drawn from the results of clinical trails.

  14. Critical pathogenic steps to high risk Helicobacter pylori gastritis and gastric carcinogenesis.

    Science.gov (United States)

    Lee, Inchul

    2014-06-07

    Helicobacter pylori (H. pylori) gastritis may progress to high risk gastropathy and cancer. However, the pathological progression has not been characterized in detail. H. pylori induce persistent inflammatory infiltration. Neutrophils are unique in that they directly infiltrate into foveolar epithelium aiming the proliferative zone specifically. Neutrophilic proliferative zone foveolitis is a critical pathogenic step in H. pylori gastritis inducing intensive epithelial damage. Epithelial cells carrying accumulated genomic damage and mutations show the Malgun (clear) cell change, characterized by large clear nucleus and prominent nucleolus. Malgun cells further undergo atypical changes, showing nuclear folding, coarse chromatin, and multiple nucleoli. The atypical Malgun cell (AMC) change is a novel premalignant condition in high risk gastropathy, which may progress and undergo malignant transformation directly. The pathobiological significance of AMC in gastric carcinogenesis is reviewed. A new diagnosis system of gastritis is proposed based on the critical pathologic steps classifying low and high risk gastritis for separate treatment modality. It is suggested that the regulation of H. pylori-induced neutrophilic foveolitis might be a future therapeutic goal replacing bactericidal antibiotics approach.

  15. Growth of Helicobacter pylori in a long spiral form does not alter expression of immunodominant proteins

    Directory of Open Access Journals (Sweden)

    Proujansky Roy

    2002-09-01

    Full Text Available Abstract Background We have previously reported that altered culture conditions (a broth media with shaking could induce a strain of Helicobacter pylori to assume a long spiral morphology resembling that described for Helicobacter heilmannii. The present study was initiated to determine if other strains of H. pylori could be induced to assume that morphology and if doing so would alter the expression of immunodominant proteins. Results The six strains used in this study were American Type Culture Collection 43504, 43579, 49503, 51652, and 51653, and Sydney Strain I. Each strain was grown on solid media and in broth culture using conditions previously shown to induce the long spiral morphology in strain 43504. DNA from each was subjected to urease gene fingerprint analysis. Results of the molecular analysis showed identical fingerprint patterns for each strain independent of culture source, indicating that only a single strain was present in each culture. Expression of immunodominant proteins was assessed by SDS polyacrylamide gel electrophoresis and Western blotting with hyperimmune rabbit anti H. pylori sera or serum from an H. pylori infected patient. Analysis of protein profiles revealed some variation between strains but no significant differences associated with morphologic alterations. Conclusions These results indicate that growth of H. pylori in a long spiral form does not affect expression of immunodominant proteins, thus in vivo growth in the long spiral form (not documented to date would not be distinguishable by serology.

  16. Ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over IFN-α in HTLV-1-associated myelopathy.

    Directory of Open Access Journals (Sweden)

    Britta Moens

    Full Text Available BACKGROUND: Clear therapeutic guidelines for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP are missing due to the lack of randomized double-blind controlled clinical trials. Moderate yet similar clinical benefit has been demonstrated for IFN-α and high-dose ascorbic acid (AA monotherapy in a large open clinical trial. However, there is a lack of in vivo and in vitro studies exploring and comparing the effects of high-dose AA and IFN-α treatment in the context of HAM/TSP. Therefore, we performed the first comparative analysis of the ex vivo and in vitro molecular and cellular mechanisms of action of IFN-α and high-dose AA in HAM/TSP. PRINCIPAL FINDINGS: Through thymidine incorporation and quantification of Th1/Th2/Th17 cytokines, we demonstrate that high-dose AA displays differential and superior antiproliferative and immunomodulatory effects over IFN-α in HAM/TSP PBMCs ex vivo. In addition, high-dose AA, but not IFN-α, induced cell death in both HAM/TSP PBMCs and HTLV-1-infected T-cell lines MT-2 and MT-4. Microarray data combined with pathway analysis of MT-2 cells revealed AA-induced regulation of genes associated with cell death, including miR-155. Since miR-155 has recently been demonstrated to up-regulate IFN-γ, this microRNA might represent a novel therapeutic target in HAM/TSP, as recently demonstrated in multiple sclerosis, another neuroinflammatory disease. On the other hand, IFN-α selectively up-regulated antiviral and immune-related genes. CONCLUSIONS: In comparison to IFN-α, high-dose AA treatment has superior ex vivo and in vitro cell death-inducing, antiproliferative and immunomodulatory anti-HTLV-1 effects. Differential pathway activation by both drugs opens up avenues for targeted treatment in specific patient subsets.

  17. Helicobacter Pylori Seropostivity of Colon Cancer

    Directory of Open Access Journals (Sweden)

    F. Tugba Kos

    2014-03-01

    Full Text Available Aim: Until now many researches have showed that Helicobacter pylori infection may be etiological factor of colorectal cancer. The aim of current study was to investigate the frequency of H.pylori infection seropositivity of colorectal cancer patients and compare the clinicopathological features of H.pylori positive patients with negative ones. Material and Method: Seventy four colorectal patients were included in study. Retrospectively, patients clinical features, surgery history and pathological characteristics were screened. Patients group serum samples were collected. H.pylori Ig G level were quantitatively measured with ELISA method and levels above 5 arbU/ml were accepted as seropositive. Results: Patients median age was 60.5 ( range 26-83 and 56.8% (n=42 were male. H.pylori Ig G was positive in 37.8% (n=28 and negative in 62.2% (n=46 of patient group. H.pylori serpositive and negative patients median age of diagnosis were 56 and 64 respectively (p=0.01. There were no significant difference between H.pylori seropositive group when compared with negative group according to age, level of CEA and Ca 19-9, stage, lymph node involvement, perineural and vascular invasion, presence of polyps, differantion, localisation of tumours. Discussion: H.pylori seropositive patients were diagnosed at younger age. Association of this finding with etiology was confusing. Further studies with healthy controls may provide detailed information about whether H.pylori seropositivity is associated with colorectal cancer etiology.

  18. 3rd BRAZILIAN CONSENSUS ON Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Luiz Gonzaga Coelho

    2013-04-01

    Full Text Available Significant progress has been obtained since the Second Brazilian Consensus Conference on Helicobacter pylori Infection held in 2004, in São Paulo, SP, Brazil, and justify a third meeting to establish updated guidelines on the current management of H. pylori infection. The Third Brazilian Consensus Conference on H pylori Infection was organized by the Brazilian Nucleus for the Study of Helicobacter, a Department of the Brazilian Federation of Gastroenterology and took place on April 12-15, 2011, in Bento Gonçalves, RS, Brazil. Thirty-one delegates coming from the five Brazilian regions and one international guest, including gastroenterologists, pathologists, epidemiologists, and pediatricians undertook the meeting. The participants were allocated in one of the five main topics of the meeting: H pylori, functional dyspepsia and diagnosis; H pylori and gastric cancer; H pylori and other associated disorders; H pylori treatment and retreatment; and, epidemiology of H pylori infection in Brazil. The results of each subgroup were submitted to a final consensus voting to all participants. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded. Seventy per cent and more votes were considered as acceptance for the final statement. This article presents the main recommendations and conclusions to guide Brazilian doctors involved in the management of H pylori infection.

  19. 3rd Brazilian Consensus on Helicobacter pylori.

    Science.gov (United States)

    Coelho, Luiz Gonzaga; Maguinilk, Ismael; Zaterka, Schlioma; Parente, José Miguel; do Carmo Friche Passos, Maria; Moraes-Filho, Joaquim Prado P

    2013-04-01

    Signicant progress has been obtained since the Second Brazilian Consensus Conference on Helicobacter pylori Infection held in 2004, in São Paulo, SP, Brazil, and justify a third meeting to establish updated guidelines on the current management of H. pylori infection. The Third Brazilian Consensus Conference on H pylori Infection was organized by the Brazilian Nucleus for the Study of Helicobacter, a Department of the Brazilian Federation of Gastroenterology and took place on April 12-15, 2011, in Bento Gonçalves, RS, Brazil. Thirty-one delegates coming from the five Brazilian regions and one international guest, including gastroenterologists, pathologists, epidemiologists, and pediatricians undertook the meeting. The participants were allocated in one of the five main topics of the meeting: H pylori, functional dyspepsia and diagnosis; H pylori and gastric cancer; H pylori and other associated disorders; H pylori treatment and retreatment; and, epidemiology of H pylori infection in Brazil. The results of each subgroup were submitted to a final consensus voting to all participants. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded. Seventy per cent and more votes were considered as acceptance for the final statement. This article presents the main recommendations and conclusions to guide Brazilian doctors involved in the management of H pylori infection.

  20. Proteomic analysis of the function of sigma factor σ54 in Helicobacter pylori survival with nutrition deficiency stress in vitro.

    Directory of Open Access Journals (Sweden)

    Yundong Sun

    Full Text Available H. pylori can survive under a nutrition-deficient environment. During infection and transmission, H. pylori is confronted with nutrient limitation and the bacterium requires rapid alteration in gene expression for survival under stress conditions. However, the mechanism underlining this regulation remains unknown. A previous study showed that σ(54 is an important regulation factor for H. pylori survival in the nutrition-deficient environment. Our results show that the expression of σ(54 (rpoN is significantly induced in the stationary phase (nutrition deficiency and the rpoN mutant showed a significantly lower viability than wild-type H. pylori in the late stationary phase. Thus, σ(54 is involved in H. pylori survival during nutrient limitation. We used comparative proteomics to analyze the protein differentiation between wild-type and rpoN mutant during the stationary phase. With depleted nutrients, σ(54 can slow the process of proliferation by negatively regulating genes involved in energy metabolism and biosynthesis and enhance stress-resistant ability by positively regulating genes involved in protein fate and redox reaction. Especially, NapA positively regulated by σ(54 plays an important function in H. pylori survival both in the stationary phase and in water, and the latter situation would be beneficial for bacterial in vitro transmission. Our investigations give new light on the adaptive regulation of H. pylori under stress conditions.

  1. Impact of cytotoxin-associated gene A of Helicobacter pylori strains on microalbuminuria in type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Ibrahim Amany

    2010-01-01

    Full Text Available Cytotoxin-associated gene A (CagA positive strains of H. pylori have a significant correlation with gastritis and peptic ulcer, and may induce persistent systemic inflammatory response, increase vascular damage, and compromise glycemic control in diabetic patients. To evaluate correlation between infection by cagA positive strains of H. pylori and occurrence of microalbuminuria and glycemic control in type 2 diabetic patients, we prospectively studied 98 dyspeptic type 2 diabetic patients as a study group and 102 dyspeptic non-diabetic subjects as a control group. Gastric biopsy specimens obtained with endoscopy were cultured to isolate H. pylori. All the isolated H. pylori strains from cultures were used for detection of cagA gene by polymerase chain reaction. There was no significant difference between study and control groups regarding infection with cagA positive strains of H. pylori ( P= 0.145. Furthermore, there was no significant differences between both groups concerning the incidence of microalbuminuria ( P= 0.145. On the other hand, there was an extremely statistically significant difference in the inci-dence of microalbuminuria and glycemic control in the diabetic patients between those infected with cagA positive strains of H. pylori and cag A negative starins (P= 0.000. We conclude that infection with cagA positive strains of H. pylori are strongly associated with the increased inci-dence of microalbuminuria and poor glycemic control in type 2 diabetic patients.

  2. Transcriptional profiling of gastric epithelial cells infected with wild type or arginase-deficient Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Kim Songhee H

    2012-08-01

    Full Text Available Abstract Background Helicobacter pylori causes acute and chronic gastric inflammation induced by proinflammatory cytokines and chemokines secreted by cells of the gastric mucosa, including gastric epithelial cells. Previous studies have demonstrated that the bacterial arginase, RocF, is involved in inhibiting T cell proliferation and CD3ζ expression, suggesting that arginase could be involved in a more general dampening of the immune response, perhaps by down-regulation of certain pro-inflammatory mediators. Results Global transcriptome analysis was performed on AGS gastric epithelial cells infected for 16 hours with a wild type Helicobacter pylori strain 26695, an arginase mutant (rocF- or a rocF+ complemented strain. H. pylori infection triggered altered host gene expression in genes involved in cell movement, death/growth/proliferation, and cellular function and maintenance. While the wild type strain stimulates host inflammatory pathways, the rocF- mutant induced significantly more expression of IL-8. The results of the microarray were verified using real-time PCR, and the differential levels of protein expression were confirmed by ELISA and Bioplex analysis. MIP-1B was also significantly secreted by AGS cells after H. pylori rocF- mutant infection, as determined by Bioplex. Even though not explored in this manuscript, the impact that the results presented here may have on the development of gastritis, warrant further research to understand the underlying mechanisms of the relationship between H. pylori RocF and IL-8 induction. Conclusions We conclude that H. pylori arginase modulates multiple host signaling and metabolic pathways of infected gastric epithelial cells. Arginase may play a critical role in anti-inflammatory host responses that could contribute to the ability of H. pylori to establish chronic infections.

  3. Identification of novel Cyclooxygenase-2-dependent genes in Helicobacter pylori infection in vivo

    Directory of Open Access Journals (Sweden)

    Wiedenmann Bertram

    2009-03-01

    Full Text Available Abstract Background Helicobacter pylori is a crucial determining factor in the pathogenesis of benign and neoplastic gastric diseases. Cyclooxygenase-2 (Cox-2 is the inducible key enzyme of arachidonic acid metabolism and is a central mediator in inflammation and cancer. Expression of the Cox-2 gene is up-regulated in the gastric mucosa during H. pylori infection but the pathobiological consequences of this enhanced Cox-2 expression are not yet characterized. The aim of this study was to identify novel genes down-stream of Cox-2 in an in vivo model, thereby identifying potential targets for the study of the role of Cox- 2 in H. pylori pathogenesis and the initiation of pre- cancerous changes. Results Gene expression profiles in the gastric mucosa of mice treated with a specific Cox-2 inhibitor (NS398 or vehicle were analysed at different time points (6, 13 and 19 wk after H. pylori infection. H. pylori infection affected the expression of 385 genes over the experimental period, including regulators of gastric physiology, proliferation, apoptosis and mucosal defence. Under conditions of Cox-2 inhibition, 160 target genes were regulated as a result of H. pylori infection. The Cox-2 dependent subset included those influencing gastric physiology (Gastrin, Galr1, epithelial barrier function (Tjp1, connexin45, Aqp5, inflammation (Icam1, apoptosis (Clu and proliferation (Gdf3, Igf2. Treatment with NS398 alone caused differential expression of 140 genes, 97 of which were unique, indicating that these genes are regulated under conditions of basal Cox-2 expression. Conclusion This study has identified a panel of novel Cox-2 dependent genes influenced under both normal and the inflammatory conditions induced by H. pylori infection. These data provide important new links between Cox-2 and inflammatory processes, epithelial repair and integrity.

  4. Helicobacter pylori neutrophil activating protein as target for new drugs against H.pylori inflammation

    Institute of Scientific and Technical Information of China (English)

    Theodora Choli-Papadopoulou; Filippos Kottakis; Georgios Papadopoulos; Stefanos Pendas

    2011-01-01

    Helicobacter pylori (H. pylori ) infection is among the most common human infections and the major risk factor for peptic ulcer disease and gastric cancer. Within this work we present the implication of C-terminal region of H. pylori neutrophil activating protein in the stimulation of neutrophil activation as well as the evidence that the C-terminal region of H. pylori activating protein is indispensable for neutrophil adhesion to endothelial cells, a step necessary to H. pylori inflammation. In addition we show that arabino galactan proteins derived from chios mastic gum, the natural resin of the plant Pistacia lentiscus var. Chia inhibit neutrophil activation in vitro .

  5. Helicobacter pylori: epidemiology and routes of transmission.

    Science.gov (United States)

    Brown, L M

    2000-01-01

    H. pylori is a common bacterium, and approximately 50 percent of the world's population has been estimated to be infected (198). Humans are the principal reservoir. The prevalence of H. pylori infection varies widely by geographic area, age, race, ethnicity, and SES. Rates appear to be higher in developing than in developed countries, with most of the infections occurring during childhood, and they seem to be decreasing with improvements in hygiene practices. H. pylori causes chronic gastritis and has been associated with several serious diseases of the gastrointestinal tract, including duodenal ulcer and gastric cancer. Since its "discovery" in 1982 by Warren and Marshall (1), H. pylori has been the topic of extensive research. A number of studies have used questionnaire components to investigate factors possibly related to the etiology of H. pylori infection. The majority of recent studies have not found tobacco use or alcohol consumption to be risk factors for H. pylori infection. Adequate nutritional status, especially frequent consumption of fruits and vegetables and of vitamin C, appears to protect against infection with H. pylori. In contrast, food prepared under less than ideal conditions or exposed to contaminated water or soil may increase the risk. Overall, inadequate sanitation practices, low social class, and crowded or high-density living conditions seem to be related to a higher prevalence of H. pylori infection. This finding suggests that poor hygiene and crowded conditions may facilitate transmission of infection among family members and is consistent with data on intrafamilial and institutional clustering of H. pylori infection. Understanding the route of H. pylori transmission is important if public health measures to prevent its spread are to be implemented. Iatrogenic transmission of H. pylori following endoscopy is the only proven mode. For the general population, the most likely mode of transmission is from person to person, by either the

  6. Construction of hpaA gene from a clinical isolate of Helicobacter pylori and identification of fusion protein.

    Science.gov (United States)

    Mao, Ya-Fei; Yan, Jie; Li, Li-Wei; Li, Shu-Ping

    2003-07-01

    To clone hpaA gene from a clinical strain of Helicobacter pylori and to construct the expression vector of the gene and to identify immunity of the fusion protein. The hpaA gene from a clinical isolate Y06 of H.pylori was amplified by high fidelity PCR. The nucleotide sequence of the target DNA amplification fragment was sequenced after T-A cloning. The recombinant expression vector inserted with hpaA gene was constructed. The expression of HpaA fusion protein in E.coli BL21DE3 induced by IPTG at different dosages was examined by SDS-PAGE. Western blot with commercial antibody against whole cell of H.pylori as well as immunodiffusion assay with self-prepared rabbit antiserum against HpaA fusion protein were applied to determine immunity of the fusion protein. ELISA was used to detect the antibody against HpaA in sera of 125 patients infected with H.pylori and to examine HpaA expression of 109 clinical isolates of H.pylori. In comparison with the reported corresponding sequences, the homologies of nucleotide and putative amino acid sequences of the cloned hpaA gene were from 94.25-97.32 % and 95.38-98.46 %, respectively. The output of HpaA fusion protein in its expression system of pET32a-hpaA-BL21DE3 was approximately 40 % of the total bacterial proteins. HpaA fusion protein was able to combine with the commercial antibody against whole cell of H.pylori and to induce rabbit producing specific antiserum with 1:4 immunodiffusion titer after the animal was immunized with the fusion protein. 81.6 % of the serum samples from 125 patients infected with H.pylori (102/125) were positive for HpaA antibody and all of the tested isolates of H.pylori (109/109) were detectable for HpaA. A prokaryotic expression system with high efficiency of H.pylori hpaA gene was successfully established. The HpaA expressing fusion protein showed satisfactory immunoreactivity and antigenicity. High frequencies of HpaA expression in different H.pylori clinical strains and specific antibody

  7. Antiadhesion and anti-inflammation effects of noni (Morinda citrifolia) fruit extracts on AGS cells during Helicobacter pylori infection.

    Science.gov (United States)

    Huang, Hsin-Lun; Ko, Chien-Hui; Yan, Yeong-Yu; Wang, Chin-Kun

    2014-03-19

    Helicobacter pylori is a human gastric pathogen that adheres to host cells and injects cytotoxin-associated gene A (CagA) to induce interleukin-8 (IL-8), inducible nitric oxide (iNOS), and cyclooxygenase 2 (COX-2). Noni (Morinda citrifolia) is found to possess antibacteria, anti-inflammation, and antioxidation activities, but its effect on H. pylori infection is still unknown. Ethanol and ethyl acetate extracts of noni fruit were used in this study. The inhibitory effect on CagA and H. pylori-induced IL-8, iNOS, and COX-2 were determined. The coculture medium was collected for measuring neutrophil chemotaxis. Both extracts of noni fruit showed weak inhibition on H. pylori. Both ethanol and ethyl acetate extracts provided antiadhesion of H. pylori to AGS cells and down-regulation on the CagA, IL-8, COX-2, and iNOS expressions. Results also indicated both extracts relieved neutrophil chemotaxis. Noni fruit extracts down-regulated inflammatory responses during H. pylori infection, and the phenolic compounds play key role in antiadhesion.

  8. Expression of cytokeratins in Helicobacter pylori-associated chronic gastritis of adult patients infected with cagA + strains: An immunohistochemical study

    Institute of Scientific and Technical Information of China (English)

    Vera Todorovic; Aleksandra Sokic-Milutinovic; Neda Drndarevic; Marjan Micev; Olivera Mlitrovic; Ivan Nikolic; Thomas Wex; Tomica Milosavljevic; Peter Malfertheiner

    2006-01-01

    AIM: To investigate the expression of different cytokeratins (CKs) in gastric epithelium of adult patients with chronic gastritis infected with Helicobacter pylori(H pylori) cagA + strains.METHODS: The expression of CK 7, 8, 18, 19 and 20 was studied immunohistochemically in antral gastric biopsies of 84 patients. All the CKs were immunostained in cagA +H pylori gastritis (57 cases), non-Hpylori gastritis (17 cases) and normal gastric mucosa (10 cases).RESULTS: In cagA+ Hpylori gastritis, CK8 was expressed comparably to the normal antral mucosa from surface epithelium to deep glands. Distribution of CK18 and CK 19 was unchanged, i.e. transmucosal,but intensity of the expression was different in foveolar region in comparison to normal gastric mucosa. Cytokeratin 18 immunoreactivity was significantly higher in the foveolar epithelium of H pylori-positive gastritis compared to both Hpylori-negative gastritis and controls.On the contrary, decrease in CK19 immunoreactivity occurred in foveolar epithelium of H pylori-positive gastritis. In both normal and inflamed antral mucosa without H pylori infection, CK20 was expressed strongly/ moderately and homogenously in surface epithelium and upper foveolar region, but in H pylori-induced gastritis significant decrease of expression in foveolar region was noted. Generally, in both normal antral mucosa and H pylori-negative gastritis, expression of CK7 was not observed, while in about half cagA+ H pylori-infected patients, moderate focal CK7 immunoreactivity of the neck and coiled gland areas was registered, especially in areas with more severe inflammatory infiltrate.CONCLUSION: Alterations in expression of CK 7, 18,19 and 20 together with normal expression of CK8 occur in antral mucosa of H pylori-associated chronic gastritis in adult patients infected with cagA+ strains. Alterations in different cytokeratins expression might contribute to weakening of epithelial tight junctions observed in H pylori-infected gastric mucosa.

  9. Cytotoxic T Cells in H. pylori-Related Gastric Autoimmunity and Gastric Lymphoma

    Directory of Open Access Journals (Sweden)

    Mathijs P. Bergman

    2010-01-01

    Full Text Available Helicobacter pylori infection is the major cause of gastroduodenal pathologies, but only a minority of infected patients develop gastric B-cell lymphoma, gastric autoimmunity, or other life threatening diseases, as gastric cancer or peptic ulcer. The type of host immune response against H. pylori, particularly the cytolytic effector functions of T cells, is crucial for the outcome of the infection. T cells are potentially able to kill a target via different mechanisms, such as perforins or Fas-Fas ligand interaction. In H. pylori-infected patients with gastric autoimmunity cytolytic T cells, that cross-recognize different epitopes of H. pylori proteins and H+K+-ATPase autoantigen, infiltrate the gastric mucosa and lead to gastric atrophy via long-lasting activation of Fas ligand-mediated appotosis and perforin-induced cytotoxicity. On the other hand, gastric T cells from MALT lymphoma exhibit defective perforin- and Fas-Fas ligand-mediated killing of B cells, with consequent abnormal help for B-cell proliferation, suggesting that deregulated and exhaustive H. pylori-induced T cell-dependent B-cell activation can support both the onset and the promotion of low-grade B-cell lymphoma.

  10. Regulation of Noxa-mediated apoptosis in Helicobacter pylori-infected gastric epithelial cells.

    Science.gov (United States)

    Rath, Suvasmita; Das, Lopamudra; Kokate, Shrikant Babanrao; Pratheek, B M; Chattopadhyay, Subhasis; Goswami, Chandan; Chattopadhyay, Ranajoy; Crowe, Sheila Eileen; Bhattacharyya, Asima

    2015-03-01

    Helicobacter pylori induces the antiapoptotic protein myeloid cell leukemia 1 (Mcl1) in human gastric epithelial cells (GECs). Apoptosis of oncogenic protein Mcl1-expressing cells is mainly regulated by Noxa-mediated degradation of Mcl1. We wanted to elucidate the status of Noxa in H. pylori-infected GECs. For this, various GECs such as AGS, MKN45, and KATO III were either infected with H. pylori or left uninfected. The effect of infection was examined by immunoblotting, immunoprecipitation, chromatin immunoprecipitation assay, in vitro binding assay, flow cytometry, and confocal microscopy. Infected GECs, surgical samples collected from patients with gastric adenocarcinoma as well as biopsy samples from patients infected with H. pylori showed significant up-regulation of both Mcl1 and Noxa compared with noninfected samples. Coexistence of Mcl1 and Noxa was indicative of an impaired Mcl-Noxa interaction. We proved that Noxa was phosphorylated at Ser(13) residue by JNK in infected GECs, which caused cytoplasmic retention of Noxa. JNK inhibition enhanced Mcl1-Noxa interaction in the mitochondrial fraction of infected cells, whereas overexpression of nonphosphorylatable Noxa resulted in enhanced mitochondria-mediated apoptosis in the infected epithelium. Because phosphorylation-dephosphorylation can regulate the apoptotic function of Noxa, this could be a potential target molecule for future treatment approaches for H. pylori-induced gastric cancer.

  11. Methods to monitor autophagy in H. pylori vacuolating cytotoxin A (VacA)-treated cells.

    Science.gov (United States)

    Raju, Deepa; Jones, Nicola L

    2010-01-01

    Helicobacter pylori is a gram negative pathogen that infects at least half of the world's population and is associated not only with gastric cancer but also with other diseases such as gastritis and peptic ulcers. Indeed, H. pylori is considered the single most important risk factor for the development of gastric cancer. The vacuolating cytotoxin VacA, secreted by H. pylori, promotes intracellular survival of the bacterium and modulates host immune responses. In a recent study, we reported that VacA induces autophagy. Multilamellar autophagosomes are detected in gastric epithelial cells that are distinct from the large vacuoles formed by VacA. Furthermore, inhibition of autophagy stabilizes VacA and reduces vacuolation in the cells indicating that the toxin is being degraded by autophagy, thus limiting toxin-induced host cell damage. Many of the methods that were used for this study are commonly employed techniques that were adapted for H. pylori infection and VacA intoxication. In this paper, we describe the various methods and specific protocols used for the assessment and monitoring of autophagy during H. pylori infection.

  12. Gastric expression of IL-17A and IFNγ in Helicobacter pylori infected individuals is related to symptoms.

    Science.gov (United States)

    Adamsson, Jenni; Ottsjö, Louise Sjökvist; Lundin, Samuel B; Svennerholm, Ann-Mari; Raghavan, Sukanya

    2017-07-03

    Chronic infection with Helicobacter pylori leads to gastritis and in a subpopulation of infected individuals to ulcers and cancer. Bacterial virulence factors and host immune inflammatory responses are risk factors related to disease. CD4(+) T cells secrete cytokines that promote inflammation and an anti-bacterial response in the gastric mucosa during infection. The aim of the study was to investigate the pattern of expression of CD4(+) T cell derived cytokines, IL-17A and IFNγ in paired antrum and corpus biopsies and correlate it to H. pylori infection outcome. Gene and protein expression of IL-17A and IFNγ was analyzed in gastric biopsies from H. pylori infected subjects with non-ulcer dyspepsia (NUD) or gastric ulcer; and for comparison uninfected individuals. Upregulation of IL-17A and IFNγ gene expression was seen in corpus and antrum biopsies of H. pylori infected individuals with NUD compared to in uninfected controls. The expression of these cytokines correlated significantly with each other. Immunofluorescence staining revealed increased frequencies of IL-17A(+) and IFNγ(+) cells in antrum biopsies of gastric ulcer patients compared to of H. pylori infected NUD individuals; positive cells were not detected in any of the biopsies of uninfected controls. The frequencies of IFNγ and IL-17A(+) cells correlated positively with inflammation in the antrum, but not the corpus, of H. pylori infected individuals. In the antrum, while there was no significant evidence of correlation between IFNγ and bacterial score, a positive correlation between bacterial score and IL-17A(+) cells was seen. In H. pylori infected individuals, the frequencies of IFNγ and IL-17A(+) cells were increased in the antrum, particularly in patients with H. pylori induced gastric ulcers. Even though H. pylori colonized both the corpus and antrum regions of the stomach, the cytokine responses and subsequent pathology were mainly detected in the antrum. Copyright © 2017 Elsevier Ltd. All

  13. Helicobacter pylori Disrupts Host Cell Membranes, Initiating a Repair Response and Cell Proliferation

    Directory of Open Access Journals (Sweden)

    Hsueh-Fen Juan

    2012-08-01

    Full Text Available Helicobacter pylori (H. pylori, the human stomach pathogen, lives on the inner surface of the stomach and causes chronic gastritis, peptic ulcer, and gastric cancer. Plasma membrane repair response is a matter of life and death for human cells against physical and biological damage. We here test the hypothesis that H. pylori also causes plasma membrane disruption injury, and that not only a membrane repair response but also a cell proliferation response are thereby activated. Vacuolating cytotoxin A (VacA and cytotoxin-associated gene A (CagA have been considered to be major H. pylori virulence factors. Gastric cancer cells were infected with H. pylori wild type (vacA+/cagA+, single mutant (ΔvacA or ΔcagA or double mutant (ΔvacA/ΔcagA strains and plasma membrane disruption events and consequent activation of membrane repair components monitored. H. pylori disrupts the host cell plasma membrane, allowing localized dye and extracellular Ca2+ influx. Ca2+-triggered members of the annexin family, A1 and A4, translocate, in response to injury, to the plasma membrane, and cell surface expression of an exocytotic maker of repair, LAMP-2, increases. Additional forms of plasma membrane disruption, unrelated to H. pylori exposure, also promote host cell proliferation. We propose that H. pylori activation of a plasma membrane repair is pro-proliferative. This study might therefore provide new insight into potential mechanisms of H. pylori-induced gastric carcinogenesis.

  14. Oxidative and nitrosative stress enzymes in relation to nitrotyrosine in Helicobacter pylori-infected humans

    Institute of Scientific and Technical Information of China (English)

    Anders; Elfvin; Anders; Edebo; Peter; Hallersund; Anna; Casselbrant; Lars; Fndriks

    2014-01-01

    AIM: To compare a possible relation between Helicobacter pylori(H. pylori) and the oxygen- and nitrogen radical system in humans. METHODS: Mechanisms for H. pylori to interfere with the oxygen and nitrogen radical system is of great importance for understanding of the H. pylori persistence and pathogenesis. Biopsies were obtained from the gastric wall of 21 individuals. Ongoing infection with H. pylori was detected using direct analyze from the biopsies using campylobacter-like organism test(CLO-test) and/or by using 14C-urea breath test. The individuals were divided in a negative H. pylori and a positive H. pylori group. Expression in the gastric mucosa of induc-ible nitric oxide syntase(iNOS), nicotinamide adenine dinucleotide phosphate-oxidase(NADPH-oxidase) myeloperoxidase(MPO), and nitrotyrosine were assessed by Western blotting.RESULTS: The individuals who undervent gastroscopy were divided in a H. pylori neg. [n = 13, m/f = 7/6, age(mean) = 39] and a H. pylori pos. group [n = 8, m/f = 5/3, age(mean) = 53]. Using western blot analysis iNOS was detected as a 130 kDa band. The iNOS expression was upregulated in the antrum of H. pylori infected individuals in comparison to the controls, mean ± SD being 12.6 ± 2.4 vs 8.3 ± 3.1, P < 0.01. There was a markedly upregulated expression of MPO in the antrum of H. pylori infected individuals in comparison to the control group without infection. In several of noninfected controls it was not possible to detect any MPO expression at all, whereas the expression was high in all the infected subjects, mean ± SD being 5.1 ± 3.4 vs 2.1 ± 1.9, P < 0.05. The NADPH-oxidase expression was analysed by detecting the NADPH-oxidase subunit p47-phox expression. P47-phox was detected as a 47 kDa band using Western blot, and showed a significantly higher expression of p47-phox in the antrum of the H. pylori infected individuals compared to the controls, mean ± SD being 3.1 ± 2.2 vs 0.3 ± 0.2, P < 0.01. Regarding nitrotyrosine

  15. Helicobacter pylori colonization of the oral cavity: A milestone discovery.

    Science.gov (United States)

    Yee, John K C

    2016-01-14

    Over the past several years, the severity of Helicobacter pylori (H. pylori) infections has not significantly diminished. After successful eradication, the annual H. pylori recurrence rate is approximately 13% due to oral H. pylori infection. Established clinical diagnostic techniques do not identify an oral etiologic basis of H. pylori prior to gastric infection. There has been disagreement as to whether oral infection of H. pylori exists or not, with no definite conclusion. In medical practice, negative results with the urea breath test suggest that the stomach infection of H. pylori is cured in these patients. In fact, patients can present negative urea breath test results and yet exhibit H. pylori infection due to oral infection. The present paper provides evidence that H. pylori oral infection is nonetheless present, and the oral cavity represents a secondary site for H. pylori colonization.

  16. Helicobacter pylori colonization of the oral cavity: A milestone discovery

    Science.gov (United States)

    Yee, John KC

    2016-01-01

    Over the past several years, the severity of Helicobacter pylori (H. pylori) infections has not significantly diminished. After successful eradication, the annual H. pylori recurrence rate is approximately 13% due to oral H. pylori infection. Established clinical diagnostic techniques do not identify an oral etiologic basis of H. pylori prior to gastric infection. There has been disagreement as to whether oral infection of H. pylori exists or not, with no definite conclusion. In medical practice, negative results with the urea breath test suggest that the stomach infection of H. pylori is cured in these patients. In fact, patients can present negative urea breath test results and yet exhibit H. pylori infection due to oral infection. The present paper provides evidence that H. pylori oral infection is nonetheless present, and the oral cavity represents a secondary site for H. pylori colonization. PMID:26811613

  17. Immune response to H pylori

    Institute of Scientific and Technical Information of China (English)

    Giovanni Suarez; Victor E Reyes; Ellen J Beswick

    2006-01-01

    The gastric mucosa separates the underlying tissue from the vast array of antigens that traffic through the stomach lumen. While the extreme pH of this environment is essential in aiding the activation of enzymes and food digestion, it also renders the gastric epithelium free from bacterial colonization, with the exception of one important human pathogen, H pylori. This bacterium has developed mechanisms to survive the harsh environment of the stomach, actively move through the mucosal layer,attach to the epithelium, evade immune responses, and achieve persistent colonization. While a hallmark of this infection is a marked inflammatory response with the infiltration of various immune cells into the infected gastric mucosa, the host immune response is unable to clear the infection and may actually contribute to the associated pathogenesis. Here, we review the host responses involved during infection with H pylori and how they are influenced by this bacterium.

  18. The Immunomodulator VacA Promotes Immune Tolerance and Persistent Helicobacter pylori Infection through Its Activities on T-Cells and Antigen-Presenting Cells

    Directory of Open Access Journals (Sweden)

    Aleksandra Djekic

    2016-06-01

    Full Text Available VacA is a pore-forming toxin that has long been known to induce vacuolization in gastric epithelial cells and to be linked to gastric disorders caused by H. pylori infection. Its role as a major colonization and persistence determinant of H. pylori is less well-understood. The purpose of this review is to discuss the various target cell types of VacA and its mechanism of action; specifically, we focus on the evidence showing that VacA targets myeloid cells and T-cells to directly and indirectly prevent H. pylori-specific T-cell responses and immune control of the infection. In particular, the ability of VacA-proficient H. pylori to skew T-cell responses towards regulatory T-cells and the effects of Tregs on H. pylori chronicity are highlighted. The by-stander effects of VacA-driven immunomodulation on extragastric diseases are discussed as well.

  19. Effect of the oral intake of probiotic Pediococcus acidilactici BA28 on Helicobacter pylori causing peptic ulcer in C57BL/6 mice models.

    Science.gov (United States)

    Kaur, Baljinder; Garg, Neena; Sachdev, Atul; Kumar, Balvir

    2014-01-01

    Probiotic lactic acid bacteria are being proposed to cure peptic ulcers by reducing colonization of Helicobacter pylori within the stomach mucosa and by eradicating already established infection. In lieu of that, in vitro inhibitory activity of pediocin-producing probiotic Pediococcus acidilactici BA28 was evaluated against H. pylori by growth inhibition assays. Further, chronic gastritis was first induced in two groups of C57BL/6 mice by orogastric inoculation with H. pylori with polyethylene catheter, and probiotic P. acidilactici BA28 was orally administered to study the eradication and cure of peptic ulcer disease. H. pylori and P. acidilactici BA28 were detected in gastric biopsy and fecal samples of mice, respectively. A probiotic treatment with P. acidilactici BA28, which is able to eliminate H. pylori infection and could reverse peptic ulcer disease, is being suggested as a co-adjustment with conventional antibiotic treatment. The study provided an evidence of controlling peptic ulcer disease, by diet mod

  20. Helicobacter pylori infection and serum ferritin

    DEFF Research Database (Denmark)

    Berg, Gabriele; Bode, G; Blettner, M

    2001-01-01

    OBJECTIVE: Helicobacter pylori may possibly affect the iron metabolism by occult bleeding, impaired absorption of non-hem iron, and by scavenging hem iron or ferritin, as some studies have suggested. The aim of this study was to analyze the association between H. pylori infection and serum ferrit...

  1. Helicobacter Pylori and Gastric Cancer: Clinical Aspects

    Directory of Open Access Journals (Sweden)

    Zhi-Qiang Song

    2015-01-01

    Full Text Available Objective: Although Helicobacter pylori (H. pylori is considered as the main etiological factor for gastric cancer, the strategy of screening and treating the oncogenic bacterium is still controversial. The objective was to evaluate the status and progress of the cognition about the relationship between H. pylori infection and gastric cancer from a clinical aspect. Data Sources: The data used in this review were mainly from the PubMed articles published in English from 1984 to 2015. Study Selection: Clinical research articles were selected mainly according to their level of relevance to this topic. Results: Gastric cancer is the fifth most common malignancy and the third leading cause of cancer deaths worldwide. The main etiological factor for gastric cancer is H. pylori infection. About 74.7-89.0% gastric cancer was related to H. pylori infection. Up to date, some regional gastric cancer prevention programs including the detection and treatment of H. pylori infection are under way. Current data obtained from the randomized controlled trials suggest that population-based H. pylori screening and treatment is feasible and cost-effective in preventing gastric cancer; however, a population-based H. pylori eradication campaign would potentially lead to bacterial resistance to the corresponding antibiotics, as well as a negative impact on the normal flora. Conclusions: The important questions of feasibility, program costs, appropriate target groups for intervention, and the potential harm of mass therapy with antibiotics must first be answered before implementing any large-scale program.

  2. Helicobacter pylori: From Infection to Cure

    Directory of Open Access Journals (Sweden)

    ABR Thomson

    1996-01-01

    Full Text Available Over 380 abstracts, presentations and posters of recent advances were highlighted at the European and International Helicobacter pylori meeting held July 7 to 9, 1995 in Edinburgh, Scotland. New advances abound, with major interest focusing on the simple, safe, inexpensive new `gold standard’ for H pylori eradication therapy: a single week of tid omeprazole 20 mg, metronidazole 400 mg and clarithromycin 250 mg, or omeprazole 20 mg, amoxicillin 1000 mg and clarithromycin 500 mg. To avoid false negative results, two biopsies must be taken from the antrum and two from the gastric body at least four weeks after completion of eradication therapy, and ideally should be supplemented with at least one further H pylori test such as a biopsy for urease activity or culture, or a urea breath test. While most patients with a gastric or duodenal ulcer (DU who do not consume nonsteroidal anti-inflammatory drugs are infected with H pylori, the association is much less apparent in those with a DU who present with an upper gastrointestinal hemorrhage. H pylori eradication for nonulcer dyspepsia is not widely recommended, and the patient with a DU given effective H pylori eradication who presents with dyspepsia likely has erosive esophagitis rather than recurrent DU or H pylori. Gastroenterologists are at increased risk of H pylori infection, particularly older gastroenterologists who are very busy endoscopists.

  3. Alcohol consumption and Helicobacter pylori infection

    DEFF Research Database (Denmark)

    Brenner, H; Berg, Gabriele; Lappus, N

    1999-01-01

    Alcohol has strong antimicrobial activity and stimulates gastric acid secretion. Alcohol consumption may therefore compromise the living conditions of Helicobacter pylori in the stomach. We assessed the relation of alcohol consumption with H. pylori infection among 1,785 participants ages 18...

  4. Essential role of ferritin Pfr in Helicobacter pylori iron metabolism and gastric colonization.

    Science.gov (United States)

    Waidner, Barbara; Greiner, Stefan; Odenbreit, Stefan; Kavermann, Holger; Velayudhan, Jyoti; Stähler, Frank; Guhl, Johannes; Bissé, Emmanuel; van Vliet, Arnoud H M; Andrews, Simon C; Kusters, Johannes G; Kelly, David J; Haas, Rainer; Kist, Manfred; Bereswill, Stefan

    2002-07-01

    The reactivity of the essential element iron necessitates a concerted expression of ferritins, which mediate iron storage in a nonreactive state. Here we have further established the role of the Helicobacter pylori ferritin Pfr in iron metabolism and gastric colonization. Iron stored in Pfr enabled H. pylori to multiply under severe iron starvation and protected the bacteria from acid-amplified iron toxicity, as inactivation of the pfr gene restricted growth of H. pylori under these conditions. The lowered total iron content in the pfr mutant, which is probably caused by decreased iron uptake rates, was also reflected by an increased resistance to superoxide stress. Iron induction of Pfr synthesis was clearly diminished in an H. pylori feoB mutant, which lacked high-affinity ferrous iron transport, confirming that Pfr expression is mediated by changes in the cytoplasmic iron pool and not by extracellular iron. This is well in agreement with the recent discovery that iron induces Pfr synthesis by abolishing Fur-mediated repression of pfr transcription, which was further confirmed here by the observation that iron inhibited the in vitro binding of recombinant H. pylori Fur to the pfr promoter region. The functions of H. pylori Pfr in iron metabolism are essential for survival in the gastric mucosa, as the pfr mutant was unable to colonize in a Mongolian gerbil-based animal model. In summary, the pfr phenotypes observed give new insights into prokaryotic ferritin functions and indicate that iron storage and homeostasis are of extraordinary importance for H. pylori to survive in its hostile natural environment.

  5. Helicobacter pylori cagA and vacA genes in dyspeptic Ghanaian patients.

    Science.gov (United States)

    Archampong, Timothy N; Asmah, Richard H; Aidoo, Ebenezer K; Wiredu, Edwin K; Gyasi, Richard K; Adjei, David N; Beleza, Sandra; Bayliss, Christopher D; Krogfelt, Karen

    2017-06-27

    Helicobacter pylori infection is prevalent in Ghana. The development of gastro-duodenal disease is dependent on virulence of the infecting strain, host susceptibility and environmental factors. Helicobacter pylori cagA and vacA strains induce more inflammation, ulceration and oncogenesis. Here, for the first time we present data on H. pylori cagA and vacA genes and their association with gastro-duodenal disease in Ghana. A total of 159 patients with dyspepsia at Korle-Bu Teaching Hospital, Accra, were investigated for H. pylori with urease-CLO, of which 113 (71.1%) were positive. Genomic DNA was extracted from antral biopsies using QIAGEN DNeasy kit. Detection of H. pylori vacA and cagA genes were determined by PCR as previously described. In total, 110 (69.2%) vacAs1, 71 (44.7%) vacAm1, 35 (22.0%) vacAm2, 77 (48.4%) cagA-(hydrophilic region) and 109 (68.6%) cagA-(internal duplication region) were detected. In multivariate analysis, duodenal ulcer was more likely than other diagnoses to have detectable cagA-(hydrophilic region) (OR 3.1 CI 1.2-7.9) or vacAs1m1 (OR 6.5 CI 1.2-34.0). Majority of biopsies were colonized with H. pylori harboring both cagA and vacA. H. pylori cagA-(internal duplication region) was more prevalent than cagA-(hydrophilic region). Duodenal ulcer was more likely than other diagnoses to have detectable cagA-(hydrophilic region) or vacAs1m1.

  6. Helicobacter pylori and microRNAs: Relation with innate immunity and progression of pre