Helicobacter pylori-induced tyrosine phosphorylation of IKKβ contributes to NF-κB activation

2011 ◽  
Vol 392 (4) ◽  
Author(s):  
Cornelia Rieke ◽  
Anja Papendieck ◽  
Olga Sokolova ◽  
Michael Naumann
Keyword(s):  
Helicobacter Pylori ◽  
Tyrosine Phosphorylation ◽  
Nuclear Factor Κb ◽  
Gastric Diseases ◽  
Catalytic Subunits ◽  
Proinflammatory Mediators ◽  
Iκb Kinase ◽  
Infected Cells ◽  
H Pylori ◽  
Interfering Rna

Abstract Helicobacter pylori, the etiological agent of several human gastric diseases, induces the transcription factor nuclear factor-κB (NF-κB) in colonized epithelial cells leading to the release of proinflammatory mediators. Activation of NF-κB involves the IκB kinase (IKK)-complex composed of two catalytic subunits, IKKα and IKKβ, and a regulatory scaffold protein, IKKγ. IKKβ was shown to be essential for NF-κB activation in response to a variety of stimuli including H. pylori. In addition to the phosphorylation of serine residues, tyrosine phosphorylation could be crucial for IKKβ activation. Here we provide evidence that IKKβ phosphorylation is induced in lipid rafts (DRM fractions) of H. pylori-infected cells, but not TNFα-stimulated cells. Furthermore, H. pylori transiently induces binding of IKKβ to c-Src kinase. Inhibition of c-Src by specific inhibitors as well as knockdown of c-Src by small interfering RNA reduced phosphorylation of IκBα as well as of p65. Thus, tyrosine-phosphorylated IKKβ contributes at least in part to NF-κB activation in response to H. pylori infection.

Analysis of babA, cagE and cagA Genes in Helicobacter pylori from Upper Gastric Patients in the North of Iran

2019 ◽  
Vol 19 (3) ◽  
pp. 274-278 ◽  
Author(s):  
Saba Fakhrieh Asl ◽  
Mehrnaz Pourvahedi ◽  
Ali Mojtahedi ◽  
Mohammad Shenagari
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Diseases ◽  
Specific Primers ◽  
The North ◽  
Different Types ◽  
North Of Iran ◽  
Gastric Biopsies ◽  
Pcr Method ◽  
Non Ulcer Dyspepsia ◽  
H Pylori

Objective:Helicobacter pylori is a Gram-negative bacterium which has a serious effect on up to half of the world’s population and has been related to different gastric diseases. The goal of this study was to assess the frequency of babA, cagE and cagA genotypes among H. pylori strains isolated from gastric biopsies of endoscopic patients in the north of Iran.Methods:The present study was performed on 90 strains of H. pylori isolated from patients with gastric diseases (Gastric ulcer (GU), Duodenal ulcer (DU), Gastritis (G), Non-ulcer dyspepsia (NUD) and Gastric adenocarcinoma (GC)). DNA was extracted from all isolated strains and PCR method was performed to detect the prevalence of babA2, cagE and cagA genes using specific primers.Results:Among 90 samples of H. pylori, babA2, cagE, and cagA genes were detected in 42.2%, 30% and 82.2% of strains respectively. The statistical analysis showed that the prevalence of cagA gene in GU, G, DU, and NUD was significantly higher than other genes. Moreover, cagA, and babA2 genes were significantly more prevalent in GC patients compared to cagE gene. Our isolates exhibited 8 distinct arrangements of virulence patterns. The occurrence of cagA (35.6%) was the most prevalent pattern followed by cagA/babA2 (20%) and cagA/babA2/cagE (14.4%).Conclusion:In summary, as first report from Guilan province in the north of Iran, we showed significant association between the presence of babA2, cagE, and cagA genes in different types of gastric disorders.

Perfil Epidemiológico de Pacientes Submetidos à Biópsia Gástrica em um Hospital Escola do Sul de Minas Gerais/ Epidemiological Profile of Patients Undergo Gastric Biopsy in a School Hospital of Minas Gerais

1970 ◽  
Vol 4 (3) ◽  
pp. 48-57
Author(s):  
Isabela Maria A. Ribeiro Simões ◽  
Ana Carolina Mauad Coli ◽  
Roseane de Souza Candido Irulegui
Keyword(s):  
Helicobacter Pylori ◽  
Age Groups ◽  
Epidemiological Data ◽  
Minas Gerais ◽  
Gastric Biopsy ◽  
Gastric Ulcers ◽  
Histopathological Diagnosis ◽  
Gastric Diseases ◽  
H Pylori ◽  
Epidemiological Profile

Objetivo: Determinar a prevalência de lesões benignas e neoplasia gástrica através do estudo de biópsias realizadas em um Hospital Escola do Sul de Minas Gerais, no período entre 2007 e 2011. Materiais e Métodos: A pesquisa documental foi quantitativa e retrospectiva, baseada na análise dos registros de biópsias e prontuários. Realizou-se o levantamento de dados referentes à idade, gênero, cor, profissão, diagnóstico histopatológico e presença de Helicobacter pylori nas amostras. Resultados: O número total de biópsias gástricas analisadas foi de 1225, cujo perfil populacional encontrado foi: idade média de 56,75 anos, sexo masculino (52%), cor branca (81,9 %), aposentado (30%). Os diagnósticos mais frequentes foram: gastrites (71,9%), pólipos (14,2%), adenocarcinomas (5,9%), úlceras gástricas (6%), linfomas (0,4%), sem alterações (0,4%) e outros (1,2%). Em outros, encontram-se achados de malignidade, metaplasia e xantelasma gástrico. Em relação à presença de Helicobacter pylori nas amostras, o resultado encontrado foi de24% positivas, 46% negativas e 30% não pesquisadas. Conclusão: Os resultados confirmam a alta frequência das doenças gástricas e sua incidência nas diversas faixas etárias, além do envolvimento do H. pylori em tais afecções. É de grande importância a caracterização dos dados epidemiológicos, o que permite prováveis direcionamentos para programas de prevenção e informação para a população. Palavras-chave: biópsia gástrica, gastropatia, perfil epidemiológico.  ABSTRACTObjective: To determine the prevalence of benign lesions and gastric cancer through study of biopsies performed at a school hospital in southern Minas Gerais, in the period between 2007 and 2011.Materials and Methods: The research was quantitative and retrospective, based on analysis of biopsies records and medical records. We conducted the survey data regarding age, sex, color, profession, histopathological diagnosis and the presence of Helicobacter pylori in the samples. Results: The total number of gastric biopsies analyzed was 1225. Population listing was found: mean age of 56.75 years, male (52%), white (81.9%), retired (30%). The most frequent diagnoses were gastritis (71.9%), polyps (14.2%), adenocarcinomas (5.9%), gastric ulcers (6%), lymphoma (0.4%), unchanged (0, 4%) and others (1.2%). In others, there are: findings of malignancy, metaplasia, gastric xanthelasma. Regarding the presence of Helicobacter pylori in the sample, the result was: 24% positive, 46% negative, 30% non searched. Conclusion: The results confirm the high frequency of gastric diseases and their incidence in the various age groups additionally to the involvement of H. pylori in such conditions. It is of great importance to characterize the epidemiological data, allowing probable directions for prevention and information programs for population. Keywords: gastric biopsy, gastropathy, epidemiological profile

scholarly journals The correlation between lncRNAs and Helicobacter pylori in gastric cancer

2019 ◽  
Vol 77 (9) ◽  
Author(s):  
Narges Dastmalchi ◽  
Seyed Mahdi Banan Khojasteh ◽  
Mirsaed Miri Nargesi ◽  
Reza Safaralizadeh
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Molecular Mechanisms ◽  
Gastrointestinal Diseases ◽  
Mechanisms Of Action ◽  
Molecular Pathways ◽  
Gastric Diseases ◽  
Non Coding Rnas ◽  
H Pylori ◽  
The Relationship

ABSTRACT Helicobacter pylori infection performs a key role in gastric tumorigenesis. Long non-coding RNAs (lncRNAs) have demonstrated a great potential to be regarded as effective malignancy biomarkers for various gastrointestinal diseases including gastric cancer (GC). The present review highlights the relationship between lncRNAs and H. pylori in GC. Several studies have examined not only the involvement of lncRNAs in H. pylori-associated GC progression but also their molecular mechanisms of action. Among the pertinent studies, some have addressed the effects of H. pylori infection on modulatory networks of lncRNAs, while others have evaluated the effects of changes in the expression level of lncRNAs in H. pylori-associated gastric diseases, especially GC. The relationship between lncRNAs and H. pylori was found to be modulated by various molecular pathways.

scholarly journals Annexin-A1 SUMOylation regulates microglial polarization after cerebral ischemia by modulating IKKα stability via selective autophagy

2021 ◽  
Vol 7 (4) ◽  
pp. eabc5539
Author(s):  
Xing Li ◽  
Qian Xia ◽  
Meng Mao ◽  
Huijuan Zhou ◽  
Lu Zheng ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Underlying Mechanism ◽  
Nuclear Factor Κb ◽  
Annexin A1 ◽  
Selective Autophagy ◽  
Microglial Polarization ◽  
Proinflammatory Mediators ◽  
Therapeutic Benefits ◽  
Iκb Kinase ◽  
Ikk Complex

Annexin-A1 (ANXA1) has recently been proposed to play a role in microglial activation after brain ischemia, but the underlying mechanism remains poorly understood. Here, we demonstrated that ANXA1 is modified by SUMOylation, and SUMOylated ANXA1 could promote the beneficial phenotype polarization of microglia. Mechanistically, SUMOylated ANXA1 suppressed nuclear factor κB activation and the production of proinflammatory mediators. Further study revealed that SUMOylated ANXA1 targeted the IκB kinase (IKK) complex and selectively enhanced IKKα degradation. Simultaneously, we detected that SUMOylated ANXA1 facilitated the interaction between IKKα and NBR1 to promote IKKα degradation through selective autophagy. Further work revealed that the overexpression of SUMOylated ANXA1 in microglia/macrophages resulted in marked improvement in neurological function in a mouse model of cerebral ischemia. Collectively, our study demonstrates a previously unidentified mechanism whereby SUMOylated ANXA1 regulates microglial polarization and strongly indicates that up-regulation of ANXA1 SUMOylation in microglia may provide therapeutic benefits for cerebral ischemia.

scholarly journals Helicobacter pylori Outer Membrane Vesicles and Extracellular Vesicles from Helicobacter pylori-Infected Cells in Gastric Disease Development

2021 ◽  
Vol 22 (9) ◽  
pp. 4823
Author(s):  
María Fernanda González ◽  
Paula Díaz ◽  
Alejandra Sandoval-Bórquez ◽  
Daniela Herrera ◽  
Andrew F. G. Quest
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Outer Membrane ◽  
Extracellular Vesicles ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Host Cells ◽  
Gastric Epithelium ◽  
Infected Cells ◽  
H Pylori

Extracellular vesicles (EVs) are cell-derived vesicles important in intercellular communication that play an essential role in host-pathogen interactions, spreading pathogen-derived as well as host-derived molecules during infection. Pathogens can induce changes in the composition of EVs derived from the infected cells and use them to manipulate their microenvironment and, for instance, modulate innate and adaptive inflammatory immune responses, both in a stimulatory or suppressive manner. Gastric cancer is one of the leading causes of cancer-related deaths worldwide and infection with Helicobacter pylori (H. pylori) is considered the main risk factor for developing this disease, which is characterized by a strong inflammatory component. EVs released by host cells infected with H. pylori contribute significantly to inflammation, and in doing so promote the development of disease. Additionally, H. pylori liberates vesicles, called outer membrane vesicles (H. pylori-OMVs), which contribute to atrophia and cell transformation in the gastric epithelium. In this review, the participation of both EVs from cells infected with H. pylori and H. pylori-OMVs associated with the development of gastric cancer will be discussed. By deciphering which functions of these external vesicles during H. pylori infection benefit the host or the pathogen, novel treatment strategies may become available to prevent disease.

scholarly journals Immunoglobulin light chains activate nuclear factor-κB in renal epithelial cells through a Src-dependent mechanism

Blood ◽  
2011 ◽  
Vol 117 (4) ◽  
pp. 1301-1307 ◽  
Author(s):  
Wei-Zhong Ying ◽  
Pei-Xuan Wang ◽  
Kristal J. Aaron ◽  
Kolitha Basnayake ◽  
Paul W. Sanders
Keyword(s):  
Epithelial Cells ◽  
Tyrosine Phosphorylation ◽  
Renal Injury ◽  
Src Kinase ◽  
Nuclear Factor Κb ◽  
Light Chains ◽  
Nuclear Factor ◽  
Monocyte Chemoattractant Protein 1 ◽  
Renal Epithelial Cells ◽  
Iκb Kinase

Abstract One of the major attendant complications of multiple myeloma is renal injury, which contributes significantly to morbidity and mortality in this disease. Monoclonal immunoglobulin free light chains (FLCs) are usually directly involved, and tubulointerstitial renal injury and fibrosis are prominent histologic features observed in myeloma. The present study examined the role of monoclonal FLCs in altering the nuclear factor κ light chain enhancer of activated B cells (NF-κB) activity of renal epithelial cells. Human proximal tubule epithelial cells exposed to 3 different human monoclonal FLCs demonstrated Src kinase–dependent activation of the NF-κB pathway, which increased production of monocyte chemoattractant protein-1 (MCP-1). Tyrosine phosphorylation of inhibitor of κB kinases (IKKs) IKKα and IKKβ and a concomitant increase in inhibitor of κB (IκB) kinase activity in cell lysates were observed. Time-dependent, Src kinase–dependent increases in serine and tyrosine phosphorylation of IκBα and NF-κB activity were also demonstrated. Proteasome inhibition partially blocked FLC-induced MCP-1 production. These findings fit into a paradigm characterized by FLC-induced redox-signaling events that activated the canonical and atypical (IKK-independent) NF-κB pathways to promote a proinflammatory, profibrotic renal environment.

Prospective Assessment of Helicobacter Pylori Infection and Gastric Pathologies in Sidi Bel Abbes region, Western Algeria

2018 ◽  
Vol 7 (5) ◽  
pp. 217-224
Author(s):  
Zouaouia Chama ◽  
Khedoudj Kanoun ◽  
Fatima Zohra Elkadi ◽  
Kara Turqui Douidi ◽  
Noria Harir ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Histological Study ◽  
Helicobacter Pylori Infection ◽  
University Hospital ◽  
Infection Prevalence ◽  
Gastric Diseases ◽  
Number Of Patients ◽  
H Pylori ◽  
The Impact

Helicobacter pylori infection concerns half of the world’s population, mainly in developing countries. It causes several gastrodudenal pathologies such as gastritis, ulcer and gastric adenocarcinoma. The aim of our study was to determine the prevalence of H.pylori infection and to assess the impact of different epidemiological factors as well as principal gastric diseases associ-ated to this infection. We underwent a prospective study during 18 months (month 2016-month 2017) which implicated 201 symptomatic patients for gastric fiboptic endoscopy at the level of Sidi Bel Abbes University hospital. We collected patients’ biopsies to perform a histological study and H. pylori culture. H. pylori identification was carried out based on bacteriological and biochemical analysis. The middle age of our population was (47.29 ±15.97ans) and the sex-ratio =0,8. The global prevalence of Helicobacter pylori infection is of 61.2% (123/201). This rate, after a statistic analysis, seems to be significantly related to age. It is particularly high especially for patients belonging to age range (20-30)-(51-60) years. The gender did not affect the infection prevalence that is more frequent in the gastritis case. We noticed also that HP infection prevalence was important in SBA the hospital. The range age (20-30)-(51-60) years had the highest prevalence of H. pylori and of gastritis which might be a risky ground of gastric cancer appearance. The ulcer pathology maximal rate concerned the group of 51 to 60 years. Above this age, this rate dropped whereas the number of patients suffering from gastric cancer, which presents an important rate in our study, increase for the group of 61-70 years.

scholarly journals The organization of Helicobacter pylori cag-pathogenicity island (cagPAI) genes in multiracial population with histopathological changes of gastric mucosa

2019 ◽  
Author(s):  
Alfizah Hanafiah ◽  
Shaza Azlin Razak ◽  
Hui-min Neoh ◽  
Noraziah Mohamad Zin ◽  
Bruno S. Lopes
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Pathogenicity Island ◽  
Type Iv Secretion ◽  
Virulence Determinants ◽  
Gastric Diseases ◽  
Cag Pathogenicity Island ◽  
Type Iv ◽  
Inflammatory Score ◽  
H Pylori

Abstract Background: Helicobacter pylori is a Gram-negative bacillus that colonises only the mucus layer of the human stomach and is implicated in gastric diseases. Virulent H. pylori harbouring cag-pathogenicity island (cagPAI) which encodes genes for type IV secretion system (T4SS) and CagA protein is one of the major virulence determinants involved in disease development. We examined the entire cagPAI genes in 95 H. pylori isolates from a multiracial population and examined the intactness of cagPAI region with histopathological scores of the gastric mucosa. Results: 95.8% of H. pylori isolates were cagPAI-positive with 23.2% having an intact cagPAI, whereas 72.6% had a partial/rearranged cagPAI. In our study, cag2 and cag4 were found to be significantly higher in H. pylori isolated from Malays, whereas cag4 was predominant in Chinese isolates. We also detected cag24 in significantly high proportion in isolates from the Malays and the Indians compared to the Chinese isolates. The intactness of cagPAI region showed an association with histopathological scores of the gastric mucosa. Significant association was observed between H. pylori harbouring partial cagPAI and higher density of H. pylori and neutrophil activity, whereas strains which lacked cagPAI was associated with higher inflammatory score. Conclusions: The screening of the entire cagPAI genes provides an accurate overview of the cagPAI organisation in H. pylori isolates in a multiracial population. The genotypes of H. pylori strains with various cagPAI rearrangement associated with patients’ ethnicities and histopathological scores might contribute to the pathogenesis of H. pylori infection in a multi-ethnic population.

scholarly journals Helicobacter Pylori Induce Gastric Upset

2021 ◽  
pp. 1-1
Author(s):  
Hazim Abdul Rahman Alhit
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Serum Antibody ◽  
Endoscopic Biopsy ◽  
Helicobacter Pylori Infection ◽  
Gastric Epithelium ◽  
Gastric Diseases ◽  
Heterogeneous Distribution ◽  
Cytotoxin Associated Gene A ◽  
H Pylori

Editorial: Helicobacter pylori is a micro-aerophilic, helical-form gramnegative aggressive bacteria. Accordingly, the idiom “Helico” intimates its helical appearance, “bacter” symbolizes bacteria, while “pylori” denotes stomach due to the first and common site of this bacteria living. Further, Marshall B. and Warren R. observed and described it in 1982. Then, the followed investigators studied this bacterium in detail with its consequences and complexities [1]. Gastric upset (Indigestion), dyspepsia: means impaired gastric digestion. Accordingly, the patient complains of upper abdominal pain, heartburn, belching, nausea, even feeling earlier gastric fullness than expected while eating. Furthermore, there are many causes of indigestion like gastroesophageal reflux disease, ulcer disease, gastritis, and even gastric cancer. Hence, unexplained recent onset dyspepsia in older people may need additional examinations. Moreover, one of the common causes is Helicobacter pylori infection, which needs laboratory and endoscopic examination [2]. Argument Many theories investigated the etiology and pathogenesis of Helicobacter pylori infection, concerning chronic or acute gastritis. Hence, gastric upset is the main presentation of both types of gastritis. Evidences The genotype is valuable in determining the dominant Helicobacter pylori strains as the isolates were different genetically plus heterogeneous distribution. Accordingly, the vac and cag markers operate a significant function in defining clinical consequences. These virulence agents are present in a subset of Helicobacter pylori strains isolates like cagA, iceA, vacA, and ureC. Moreover, the cagA causes cytotoxins induction by the gastric epithelial cell as Interleukin 8 [3]. The molecular intercommunication researches exhibit that the act of acarus calamus in hindering biofilm formation in Helicobacter pylori is due to the inhibitory impact of phytobio-active component, β-sitosterol, on the quorum sensing molecules-ToxB, PhnB, DnaA, plus Sip. Consequently, this opinion may suggest the molecular mechanism of Helicobacter pylori in producing the acidrelated complaints and gives a clue to a new therapy [4]. Helicobacter pylori infection causes lncRNA risk impression linked to H. pylori in gastric cancer patients and can prognosticate the prediction of these patients [5]. There was a close relationship between raised serum IgE levels in Helicobacter pylori infected patients [6]. Counterargument The laboratory investigations of Helicobacter pylori infection depend on several factors like the fluctuations of serum antibody titers in a time series, the antigene detection in stool tests, the false-positive results of lab tests, or the manner of endoscopic biopsy collection. Furthermore, other factors like the variations in Cytotoxin-Associated Gene A (CagA) in East Asian patients. Moreover, the gastric nodularity or atrophy, the patient’s age, the severity of the gastric mucosal infection are causes of variations in Helicobacter pylori detection at the time of the investigation [7]. Refutation The significant markers of H. pylori, the presence of the vacuolating cytotoxin (vacA), the cytotoxin-associated gene A (cagA), which induced by the direct communication with gastric epithelium factor antigen (iceA gene), and the presence of urease C gene (ureC). Consequently, all these factors play the principal factors in deciding the gastric consequences of Helicobacter infections. Conclusion Helicobacter pylori induce gastric upset by several mechanisms to form numerous Gastric diseases.

scholarly journals The Complete Genome Sequence of Helicobacter pylori Strain G27

2008 ◽  
Vol 191 (1) ◽  
pp. 447-448 ◽  
Author(s):  
David A. Baltrus ◽  
Manuel R. Amieva ◽  
Antonello Covacci ◽  
Todd M. Lowe ◽  
D. Scott Merrell ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Genetic Variation ◽  
Gastric Carcinoma ◽  
Genome Sequence ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Gastric Diseases ◽  
Gram Negative ◽  
H Pylori

ABSTRACT Helicobacter pylori is a gram-negative pathogen that colonizes the stomachs of over half the world's population and causes a spectrum of gastric diseases including gastritis, ulcers, and gastric carcinoma. The H. pylori species exhibits unusually high levels of genetic variation between strains. Here we announce the complete genome sequence of H. pylori strain G27, which has been used extensively in H. pylori research.

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