• pathogenesis
• rosacea
• treatment

• Humans
• Rosacea/therapy
• Rosacea/drug therapy
• Cathelicidins/therapeutic use

• IL-33
• M2 macrophages
• Th2 immunity
• eosinophils
• gastric metaplasia
• intestinal metaplasia
• spasmolytic polypeptide-expressing metaplasia (SPEM)

• DK097948 NIH HHS

• Bifidobacterium animalis
• H. pylori
• antibacterial activity
• gastric inflammation
• probiotics

• Humans
• Bifidobacterium animalis
• Helicobacter pylori
• Bifidobacterium
• Helicobacter Infections/prevention & control
• Cytokines
• Probiotics

• Shenzhen Porshealth Bioengineering Co., Ltd

• G-protein-coupled estrogen receptor
• Helicobacter pylori
• cytotoxin-associated gene A
• interleukin 8
• nuclear factor-kappa B

• Animals
• Dogs
• Humans
• Cytotoxins/metabolism
• Dog Diseases/metabolism
• Gastric Mucosa/metabolism
• GTP-Binding Proteins/metabolism
• Helicobacter Infections/metabolism
• Helicobacter Infections/veterinary
• Helicobacter pylori/genetics
• Helicobacter pylori/metabolism
• Interleukin-8/genetics
• NF-kappa B/metabolism
• Receptors, Estrogen/genetics
• Receptors, Estrogen/metabolism
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/veterinary

• Humans
• Helicobacter Infections/complications
• Helicobacter Infections/epidemiology
• Helicobacter pylori
• Stomach Neoplasms/microbiology
• Stomach Neoplasms/prevention & control
• Gastritis/complications
• Gastritis/diagnosis
• Gastritis/epidemiology
• Anti-Bacterial Agents/pharmacology
• Anti-Bacterial Agents/therapeutic use

• P01 CA116087 NCI NIH HHS
• P30 DK058404 NIDDK NIH HHS
• R01 CA077955 NCI NIH HHS
• R01 DK058587 NIDDK NIH HHS

• Apoptosis
• CMTM3
• Helicobacter pylori
• IL-8
• NEMO

Alarmins exist outside cells and are early warning signals to the immune system; as such, alarmin receptors are widely distributed on various immune cells. Alarmins, proinflammatory molecular patterns associated with tissue damage, are usually released into the extracellular space, where they induce immune responses and participate in the damage and repair processes of mucosal diseases.In the stomach, gastric alarmin release has been shown to be involved in gastric mucosal inflammation, antibacterial defense, adaptive immunity, and wound healing; moreover, this release causes damage and results in the development of gastric mucosal diseases, including various types of gastritis, ulcers, and gastric cancer. Therefore, it is necessary to understand the role of alarmins in gastric mucosal diseases. This review focuses on the contribution of alarmins, including IL33, HMGB1, defensins and cathelicidins, to the gastric mucosal barrier and their role in gastric mucosal diseases. Here, we offer a new perspective on the prevention and treatment of gastric mucosal diseases.

• Humans
• Alarmins
• HMGB1 Protein
• Cathelicidins
• Interleukin-33
• Adaptive Immunity
• Gastritis
• Gastric Mucosa
• Defensins
• Anti-Bacterial Agents

• National Natural Science Foundation of China

H. pylori is involved in the development of 80% of gastric cancers and 5.5% of all malignant conditions worldwide. Its persistence within the host’s stomach causes chronic inflammation, which is a well-known hallmark of carcinogenesis. A wide range of cytokines was reported to be involved in the initiation and long-term persistence of this local and systemic inflammation. IL-8 was among the first cytokines described to be increased in patients with H. pylori infection. Although, this cytokine was initially identified to exert a chemoattracting effect that represents a trigger for the activation of inflammatory cells within H.-pylori-infected mucosa, more recent studies failed in encountering any association between IL-8 and H. pylori infection. IL-6 is a multifunctional, pleiotropic and multipotent cytokine involved in mediating the interaction between innate and adaptive immunity with a dichotomous role acting as both a proinflammatory and an anti-inflammatory cytokine depending on the signaling pathway. IL-1α functions as a promoter of angiogenesis and vascular endothelial cell proliferation in gastric carcinoma since it is closely related to H.-pylori-induced inflammation in children. IL-1β is an essential trigger and enhancer of inflammation. The association between a low IL-1β level and an increased TNF-α level might be considered a risk factor for peptic ulcer disease in the setting of H. pylori infection. IL-10 downregulates both cytotoxic inflammatory responses and cell-mediated immune responses. H. pylori uses the immunosuppressive role of IL-10 to favor its escape from the host’s immune system. TGFβ is a continuous inflammatory mediator that promotes the adherence of H. pylori to the host’s cells and their subsequent colonization. The role of H.-pylori-induced inflammatory responses in the onset of gastric carcinogenesis seems to represent the missing puzzle piece for designing effective preventive and therapeutic strategies in patients with H.-pylori-associated gastric cancer.

The number of hypertensive population rises year by year recently, and their age becomes more youthful. For a long time, hypertension has long been regarded as a multi-factorial disease. In addition to smoking, genetics, diet and other factors, helicobacter pylori (H. pylori) had been regarded as a potential risk factor for hypertension in recent years. However, most studies had certain limitations and their results were inconsistent. Thus, it is necessary for us to assess the impact of H. pylori on hypertension through meta-analysis.

We searched all published relevant literature through multiple databases by July 23, 2021. Pooled results were calculated under the random effect model. Heterogeneity was evaluated by the Q statistic and the I² statistic. The risk of bias was evaluated via ROBINS-I tool. Publication bias was evaluated by the Egger test and Begg funnel plot.

6 eligible studies involving 11317 hypertensive patients and 12765 controls were selected from 20767 retrieval records. Our research confirmed that H. pylori significantly increased the probability of suffering from hypertension in the random effect model (OR:1.34, 95% CI:1.10–1.63, P = 0.002, I² = 74%). The same results were also found in both Asian population and developing country (OR:1.28, 95%CI:1.05–1.55, P = 0.003, I² = 78.5%).

Our results confirmed that H. pylori was a vital risk factor for hypertension. H. pylori-infected people were 13.4% higher risk for hypertension than uninfected individuals. In addition, it will be a new method to prevent and treat hypertension by eradicating H. pylori.

The registration number for systematic review in PROSPERO CRD42021279677.

• Helicobacter Infections/complications
• Helicobacter Infections/epidemiology
• Helicobacter pylori
• Humans
• Hypertension/complications
• Hypertension/epidemiology
• Risk Factors

• Xiamen medical and health Guidance project in 2020
• Medical Innovation Project of Fujian Province

• Gastritis
• Helicobacter pylori
• Inflammation
• NF-κB pathway
• Virulence genotype

• Helicobacter pylori
• cohort study
• dyslipidemia
• eradication

• Helicobacter pylori
• Nitric oxide
• biomarkers
• cytokines
• inflammation

• Gases
• Gastric Mucosa
• Helicobacter Infections
• Helicobacter pylori
• Humans
• Inflammation
• Interleukin-8
• Nitric Oxide

In Cameroon, local plants are traditionally used as remedies for a variety of ailments. In this regard, several papers report health benefits of Cameroonian spices, which include antioxidant and anti-microbial properties, whereas gastric anti-inflammatory activities have never been previously considered. The present study investigates the antioxidant and anti-inflammatory activities of hydro-alcoholic extracts of eleven Cameroonian spices in gastric epithelial cells (AGS and GES-1 cells). The extracts showed antioxidant properties in a cell-free system and reduced H₂O₂-induced ROS generation in gastric epithelial cells. After preliminary screening on TNFα-induced NF-κB driven transcription, six extracts from Xylopia parviflora, Xylopia aethiopica, Tetrapleura tetraptera, Dichrostachys glomerata, Aframomum melegueta, and Aframomum citratum were selected for further studies focusing on the anti-inflammatory activity. The extracts reduced the expression of some NF-κB-dependent pro-inflammatory mediators strictly involved in the gastric inflammatory process, such as IL-8, IL-6, and enzymes such as PTGS2 (COX-2), without affecting PTGS1 (COX-1). In conclusion, the selected extracts decreased pro-inflammatory markers by inhibiting the NF-κB signaling in gastric cells, justifying, in part, the traditional use of these spices. Other molecular mechanisms cannot be excluded, and further studies are needed to better clarify their biological activities at the gastric level.

• COX-2
• Cameroonian plants
• NF-κB
• antioxidant
• ethnopharmacology
• gastric inflammation
• interleukin 6
• interleukin 8

• Anti-Inflammatory Agents/pharmacology
• Antioxidants/pharmacology
• Cameroon
• Epithelial Cells/drug effects
• Gastric Mucosa/cytology
• Humans
• NF-kappa B/metabolism
• Plant Extracts/pharmacology
• Signal Transduction/drug effects
• Spices/analysis

Although, outer membrane protein OipA of Helicobacter pylori has been associated with gastric mucosal damage and gastroduodenal diseases, studies evaluating gastric cancer patients are scarce. We investigated whether the functional oipA “on” status was associated with gastric cancer in the North-eastern Brazil, region with high prevalence of gastric cancer.

We included samples from 95 H. pylori positive subjects (23 patients with gastritis, 24 with gastric cancer, 32 first-degree relatives of gastric cancer patients and 16 children). oipA was assayed by polymerase chain reaction (PCR) and DNA sequencing. cagA and vacA status were evaluated by PCR.

Overall 81.1% of the H. pylori strains had functional oipA. In adults, the oipA “on” status (OR = 9.20; 95%CI = 1.45–58.48, P = 0.02) and increasing age (OR = 1.08; 95%CI = 1.03–1.14; P = 0.003) were independently associated with gastric cancer in a logistic model. The oipA “on” status (OR = 14.75; 95%CI: 2.53–86.13, P = 0.003) was also associated with first-degree relatives of gastric cancer patients when compared with gastritis. The frequency of oipA “on” status did not differ between children and adults (P = 0.87). The oipA “on” status was significantly correlated with the presence of cagA and vacA s1 m1.

oipA “on” status was independently associated with gastric cancer and first-degree relatives of gastric cancer patients in North-eastern Brazil.

• Gastric cancer
• Helicobacter pylori
• cagA
• oipA
• vacA

• Gastric cancer
• Helicobacter pylori
• Immune modulation
• Immunotherapy
• Inflammation

Some studies suggest a significant relationship between Helicobacter pylori infection and atherogenesis; but the mechanism of the relationship is almost unknown. The current study aimed at evaluating the relationship between H. pylori infection and serum lipid profile.

The current study was conducted on 2573 patients, from 2008 to 2015. The serum anti-Helicobacter pylori antibody titer and serum lipid profile were assessed in the study population; data were statistically analyzed by SPSS version 16. P values < 0.05 were considered significant.

In the current study, 66.5% of the cases were serologically positive for H. pylori. Among male cases, the level of low density lipoprotein (LDL) was higher in patients with H. pylori infection, compared with that of the ones without the infection (P = 0.03); although level of triglyceride (TG) was higher and the level of high density lipoprotein (HDL) was lower in the cases with H. pylori infection; there was no statistically significant difference between the cases with and without H. pylori infection regarding the level of HDL and TG. Among female cases, the level of TG was significantly lower in patients with H. pylori infection, compared with that of the ones without the infection (P = 0.001); but there was no significant difference between the cases with and without H. pylori infection regarding the level of LDL and HDL. The mean fasting blood sugar (FBS) in the cases with H. pylori infection was significantly higher than that of the ones without the infection (P = 0.04).

According to the results of the current study, the levels of LDL and FBS were high among the male cases with H. pylori infection. However, in females with H. pylori infection the level of TG was low; hence, it seems that the atherogenicity of H. pylori affected the level of blood sugar more.

• Helicobacter pylori
• Lactobacillus fermentum UCO-979C
• gastric epithelial cells
• gastric inflammation
• macrophages

• Cell Cycle
• Cell Transformation, Neoplastic
• Gastric Juice/metabolism
• Helicobacter Infections/complications
• Helicobacter Infections/epidemiology
• Helicobacter pylori
• Humans
• Lymphoma, Non-Hodgkin/microbiology
• Models, Biological
• Stomach Neoplasms/epidemiology
• Stomach Neoplasms/microbiology
• Stomach Neoplasms/prevention & control

• Akt
• CagA
• Helicobacter pylori
• chemotherapeutics

• Helicobacter pylori
• adhesion
• complete tfs cluster
• interleukin-8
• operon
• pH

• agrimoniin
• biological activity
• chemistry
• ellagitannin
• hyphated techniques
• metabolism

• CNV
• GWAS
• Gastric cancer
• Interleukin
• Polymorphism
• mRNA expression

• deregulation and overexpression/gene inactivation
• desoxyribonucleic acid methylation
• gastric cancer
• inflammation
• polymorphisms

• Chemokines
• Cytokines
• Gastric cancer
• Growth factors
• IHC TMA
• Stroma

• Adult
• Aged
• Chemokines/biosynthesis
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Neoplasm Proteins/biosynthesis
• Prognosis
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/pathology

Interleukin (IL)-8 is the key agent for initiating an inflammatory response to infection with Helicobacter pylori. Some strains of Lactobacillus spp. are known to colonize the stomach and suppress inflammation caused by H. pylori. In this study, we characterized two gastric-derived lactobacilli, Lactobacillus salivarius (LS) strains B37 and B60, capable of inhibiting H. pylori-induced IL-8 production by gastric epithelial cells.

Conditioned media from LS-B37 and LS-B60 suppressed H. pylori-induced IL-8 production and mRNA expression from AGS cells without inhibiting H. pylori growth. These conditioned media suppressed the activation of NF-κB but did not suppress c-Jun activation. IL-8 inhibitory substances in conditioned media of LS-B37 and LS-B60 are heat-stable and larger than 100 kDa in size. The inhibitory activity of LS-B37 was abolished when the conditioned medium was treated with α-amylase but still remained when treated with either proteinase K, trypsin, lipase or lysozyme. The activity of LS-B60 was abolished when the conditioned medium was treated with either amylase or proteinase K but still remained when treated with lysozyme. Treatment with lipase and trypsin also significantly affected the inhibitory activity of LS-B60 although the conditioned medium retained IL-8 suppression statistically different from media control.

These results suggest that L. salivarius strains B37 and B60 produce different immunomodulatory factors capable of suppressing H. pylori-induced IL-8 production from gastric epithelial cells. Our results suggest that the large, heat-stable immunomodulatory substance(s) present in the LCM of LS-B37 is a polysaccharide, while the one(s) of LS-B60 is either complex consisting of components of polysaccharide, lipid and protein or includes multiple components such as glycoprotein and lipoprotein.

The online version of this article (doi:10.1186/s12866-016-0861-x) contains supplementary material, which is available to authorized users.

• Anti-inflammatory
• Helicobacter pylori
• Interleukin-8
• Lactobacillus salivarius
• Probiotic

• Helicobacter pylori
• NF-κB
• gastric epithelial cells
• interleukin-8
• psyllium

• Cell Line, Tumor
• DNA Fragmentation/drug effects
• Gastric Mucosa/cytology
• Gastric Mucosa/drug effects
• Gastric Mucosa/metabolism
• Helicobacter pylori/drug effects
• Host-Pathogen Interactions/drug effects
• Humans
• Interleukin-8/metabolism
• NF-kappa B/metabolism
• Psyllium/chemistry
• Psyllium/pharmacology

• Agrimoniin
• Casuarictin
• Ellagic acid
• Ellagitannins
• Fragaria spp
• Gastric inflammation
• IL-8
• Procyanidin B1
• Procyanidins
• Strawberry

H. pylori-induced chronic inflammation is considered the most important cause of gastric cancer. The actual process how chronic inflammation triggers gastric carcinogenesis is still not clear. In this study, neutrophils and relative markers in gastric cancer development were examined with immunohistochemistry and fluorescence RNA in situ hybridization methods. On average, 24 times more neutrophils were found in gastric cancer tissues and about 9 times more neutrophils were found in gastric intestinal metaplasia tissues comparing to normal gastric tissue controls. CagA⁺ H. pylori infection in cancer adjacent tissues or EBV infection in cancer tissues did not increase neutrophil infiltration into gastric cancer tissues significantly. Neutrophil density was positively correlated with cell proliferation while negatively correlated with E-cadherin intensity. E-cadherin is also transcriptionally downregulated in gastric cancer tissues comparing to adjacent tissue controls. The increased neutrophils in the gastric cancer tissues appear to be related to increased chemoattractant IL-8 levels. In gastric cancers, neutrophil numbers were higher comparing to cancer adjacent tissues and not associated with patient ages, tumor invasion depth, tumor staging, metastasis or cancer types. The conclusion is that persisting and increasing neutrophil infiltration is associated with E-cadherin downregulation, cell proliferation and gastric carcinogenesis.

The babA2 gene along with the cagA and vacA of Helicobacter pylori has been considered as a risk factor for the disease outcome in certain populations. This study was aimed to understand the role of babA2 of H. pylori with the background of cagA and vacA in disease manifestations in Indian sub population.

A total of 114 H. pylori strains isolated from duodenal ulcer (DU) (n = 53) and non-ulcer dyspepsia (NUD) patients (n = 61) were screened for the prevalence of these virulence markers by PCR. The comparative study of IL-8 production and apoptosis were done by co-culturing the AGS cell line with H. pylori strains with different genotypes. Adherence assay was performed with babA2 positive and negative strains. Two isogenic mutants of babA2 were constructed and the aforesaid comparative studies were carried out.

PCR results indicated that 90.6 % (48/53), 82 % (50/61) and 73.6 % (39/53) strains from DU patients were positive for cagA, vacA, and babA2, respectively. Whereas the prevalence of these genes in NUD subjects were 70.5 % (43/61); 69.8 % (37/53), and 65.6 % (39/61), respectively. Although adherence to AGS cells was comparable among strains with babA2 positive and negative genotypes, but the triple positive strains could induce highest degree of IL-8 production and apoptosis, followed by the cagA⁻/vacA⁻/babA2⁺ strains and triple negative strains, respectively. The wild type strains showed significantly higher IL-8 induction as well as apoptosis in ex vivo than its isogenic mutant of babA2.

PCR study demonstrated that there was no significant association between the distribution of babA2 genotype or of triple positive strains and disease outcome in this sub population. The adherence assay showed that there was no significant difference in the extent of adherence to AGS cells among babA2 positive and negative strains. But the ex vivo study indicated that the triple positive or even the babA2 only positive strains are involved in increased virulence. The wild type strains also exhibited increased virulence compared to the babA2 mutant strains. This inconsistency demonstrated that bacterial genotype along with host genetic polymorphisms or other factors play important role in determining the clinical manifestation of H. pylori infections.

• Adhesion molecule
• Apoptosis
• BabA2
• Duodenal ulcer
• Helicobacter pylori
• IL-8

Persistent Helicobacter pylori infection confers an increased risk for serious illnesses such as peptic ulcers and gastric cancer. Various cytokines are involved in the regulation of inflammatory immune response in H. pylori-infected gastric mucosa.

The current study aimed to obtain evidence regarding the association between IL-17, IL-8 and IL-18 expression in peripheral blood and H. pylori infection in Mongolian gerbils.

Mongolian gerbils were inoculated with H. pylori by a metal stomach catheter. After sacrifice, their gastric mucosae were examined in macroscopic, histological and electron microscopy levels. In addition, enzyme linked immunosorbent assay (ELISA) assay was performed on the IL-17, IL-8 and IL-18 cytokines in the blood samples.

Serum levels of IL-17, IL-8 and IL-18 were remarkably up-regulated compared to those of the control group. There was an obvious correlation between the increase of IL-17 and the serious extent of gastritis in the current study. However, the serum levels of IL-8 and IL-18 without getting increasingly more for repetitive intragastric administration. There were plenty of neutrophils infiltrating in the infected group mucosal. Intestinal metaplasia and gastric ulcers were also founded in H. pylori infected animals after enhanced inoculation. The edema, degeneration and necrosis changes could be found in organelles by transmission electron microscopy. More serious pathological changes were detected in the enhanced inoculation groups compared to the cycle group.

The serum levels of IL-17, but not IL-8 and IL-18 may serve as a potential biomarker for diagnosis and predicting the prognosis of gastritis caused by H. pylori.

• Helicobacter pylori
• IL-17
• Inflammation

• Bacterial Adhesion
• Bacterial Proteins/genetics
• Cell Line
• Cytokines/analysis
• DNA, Bacterial/chemistry
• DNA, Bacterial/genetics
• Endocytosis
• Enzyme-Linked Immunosorbent Assay
• Gastrointestinal Diseases/microbiology
• Gastrointestinal Diseases/pathology
• Helicobacter Infections/microbiology
• Helicobacter Infections/pathology
• Helicobacter pylori/isolation & purification
• Helicobacter pylori/pathogenicity
• Helicobacter pylori/physiology
• Humans
• Microscopy, Electron, Transmission
• Polymerase Chain Reaction
• Sequence Analysis, DNA
• Virulence
• Virulence Factors/genetics

• Adult
• Alopecia/microbiology
• Antigens, Bacterial/blood
• Bacterial Proteins/blood
• Breath Tests/methods
• Dyspepsia/epidemiology
• Dyspepsia/microbiology
• Female
• Helicobacter Infections/complications
• Helicobacter Infections/diagnosis
• Helicobacter Infections/epidemiology
• Helicobacter pylori/isolation & purification
• Humans
• Immunoglobulin G/blood
• Male
• Middle Aged
• Prospective Studies
• Turkey
• Urea/analysis
• Vitiligo/microbiology
• Young Adult

• Apoptosis
• Cathepsin X
• Gastric cancer
• Ribosomal phosphoprotein P0 (RPLP0)
• Yeast two-hybrid

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.

• Diabetes mellitus
• Cytokines
• Glucose homeostasis
• Growth
• Helicobacter pylori
• Interleukins
• Lipid metabolism
• Metabolic syndrome

• Animals
• Anti-Bacterial Agents/therapeutic use
• Blood Glucose/metabolism
• Diabetes Mellitus, Type 2/blood
• Diabetes Mellitus, Type 2/epidemiology
• Diabetes Mellitus, Type 2/microbiology
• Dyslipidemias/blood
• Dyslipidemias/epidemiology
• Dyslipidemias/microbiology
• Helicobacter Infections/blood
• Helicobacter Infections/drug therapy
• Helicobacter Infections/epidemiology
• Helicobacter Infections/microbiology
• Helicobacter pylori/drug effects
• Helicobacter pylori/growth & development
• Host-Pathogen Interactions
• Humans
• Inflammation Mediators/blood
• Insulin Resistance
• Lipids/blood
• Metabolic Syndrome/blood
• Metabolic Syndrome/epidemiology
• Metabolic Syndrome/microbiology
• Risk Factors
• Treatment Outcome

• Helicobacter pylori
• Lactobacillus plantarum
• Sprague-Dawley rat
• interleukin-8
• probiotic
• stomach

AIM: To investigate the correlation between the Helicobacter pylori (H. pylori) infection and host genetic background of healthy populations in Indonesia.

METHODS: In March 2007, epidemiological studies were undertaken on the general population of a city in Indonesia (Mataram, Lombok). The participants included 107 men and 187 women, whose ages ranged from 6 to 74 years old, with an average age of 34.0 (± 14.4) (± SD). The H. pylori of subject by UBT method determination, and through the polymerase chain reaction with confronting two-pair primers (PCR-CTPP) method parsing the single nucleotide polymorphism of interleukin (IL)-8, IL-4, IL-1β, CD14, tumor necrosis factor (TNF-α) and tyrosine-protein phosphates non-receptor type 11 (PTPN11) genotypes. The experimental data were analyzed by the statistical software SAS.

RESULTS: The H. pylori infection rates in the healthy Indonesian population studied were 8.4% for men and 12.8% for women; no obvious differences were noted for H. pylori infection rates by sex or age. TC genotypes of IL-4, TC and CC genotypes of TNF-α, and GA genotypes of PTPN11, were higher in frequency. Both CC and TC genotype of TNF-α T-1031C loci featured higher expressions in the healthy Indonesian population Indonesia studied of (OR = 1.99; 95%CI: 0.67-5.89) and (OR = 1.66; 95%CI: 0.73-3.76), respectively. C allele of IL-1β T-31C gene locus was at a higher risk (OR = 1.11; 95%CI: 0.70-1.73) of H. pylori infection, but no statistical significance was found in our study.

CONCLUSION: We reveal that the association between the TNF-α and IL-1β genotypes may be the susceptibility of H. pylori in the studied population.

• Helicobacter pylori
• Tumor necrosis factor
• Interleukin-1β
• Infection
• Allele

• Adolescent
• Adult
• Aged
• Chi-Square Distribution
• Child
• Female
• Gene Frequency
• Genetic Predisposition to Disease
• Helicobacter Infections/epidemiology
• Helicobacter Infections/genetics
• Helicobacter Infections/immunology
• Helicobacter Infections/microbiology
• Helicobacter pylori/pathogenicity
• Host-Pathogen Interactions/genetics
• Humans
• Indonesia/epidemiology
• Interleukin-1beta/genetics
• Logistic Models
• Male
• Middle Aged
• Odds Ratio
• Phenotype
• Polymorphism, Single Nucleotide
• Risk Factors
• Tumor Necrosis Factor-alpha/genetics
• Young Adult

• Bacterial Adhesion
• Bacterial Proteins/genetics
• Bacterial Proteins/pharmacology
• Biliary Tract/cytology
• Cell Line, Tumor
• Epithelial Cells/drug effects
• Epithelial Cells/metabolism
• Epithelial Cells/microbiology
• Gene Expression Regulation/drug effects
• Genomic Islands
• Helicobacter pylori/genetics
• Helicobacter pylori/metabolism
• Helicobacter pylori/physiology
• Humans
• Integrin alpha5beta1/metabolism
• Interleukin-8/biosynthesis
• Interleukin-8/metabolism
• Myeloid Differentiation Factor 88/metabolism
• NF-kappa B/biosynthesis
• Nod1 Signaling Adaptor Protein/genetics
• Nod1 Signaling Adaptor Protein/metabolism
• Toll-Like Receptors/genetics

CagA protein contributes to pro-inflammatory responses during H. pylori infection, following its intracellular delivery to gastric epithelial cells. Here, we report for the first time in an isogenic background, on the subtle role of CagA phosphorylation on terminal EPIYA-C motifs in the transcriptional activation and expression of IL-8. We utilized isogenic H. pylori mutants of P12 reference strain, expressing CagA with varying number of EPIYA-C motifs and the corresponding phosphorylation defective EPIFA-C motifs while preserving intact the CM multimerization motifs. These mutants had been previously closely scrutinized in terms of type IV secretion system functionality, CagA translocation and its subsequent phosphorylation. Following infection of gastric epithelial cell lines, transcriptional activation of IL-8 gene and secreted IL-8 levels were found to be strictly dependent upon the functionality of the EPIYA-C phosphorylation motifs, as EPIFA-C phosphorylation-deficient CagA expression failed to induce full IL-8 transcriptional activity. Interestingly, levels of IL-8 gene activation and of secreted IL-8 were the same, irrespective of the number of EPIYA-C terminal repeats. We monitored IkBα phosphorylation and confirmed CagA involvement in NF-kB activation. Furthermore, we observed that presence of EPIYA-C functional phosphorylation motifs contributed to NF-kB activation. NF-kB upstream signaling events, such as early ERK1/2 and AKT activation were confirmed to be independent of EPIYA-C phosphorylation. On the contrary, use of TAK1 specific inhibitor 5Z-7-Oxozeaenol resulted in complete arrest of IL-8 secretion, in a dose-dependent manner, irrespective of CagA status. H. pylori-infected TAK1^-/- mouse embryonic fibroblasts (MEFs) failed to induce NF-kB activity, unlike the respective control MEFs. CagA and TAK1 were found to immunoprecipitate together, irrespective of CagA EPIYA-C status, thus confirming earlier reports of TAK1 and CagA protein interaction. Our data suggest that CagA may potentially interfere with TAK1 activity during NF-kB activation for IL-8 induction in early H. pylori infection.

• Amino Acid Motifs
• Amino Acid Sequence
• Animals
• Antigens, Bacterial/chemistry
• Antigens, Bacterial/metabolism
• Antigens, Bacterial/pharmacology
• Bacterial Proteins/chemistry
• Bacterial Proteins/metabolism
• Bacterial Proteins/pharmacology
• Cell Line, Tumor
• Epithelial Cells/metabolism
• Epithelial Cells/microbiology
• Fibroblasts/metabolism
• Fibroblasts/microbiology
• Helicobacter pylori/metabolism
• Helicobacter pylori/physiology
• Humans
• Interleukin-8/genetics
• Interleukin-8/metabolism
• MAP Kinase Kinase Kinases/metabolism
• Mice
• Mitogen-Activated Protein Kinase 1/metabolism
• Mitogen-Activated Protein Kinase 3/metabolism
• Molecular Sequence Data
• NF-kappa B/metabolism
• Phosphorylation
• Proto-Oncogene Proteins c-akt/metabolism
• Repetitive Sequences, Amino Acid
• Transcriptional Activation/drug effects

• Advanced gastric cancer
• angiogenic pathway
• biomarker
• epidermal growth factor pathway
• targeted therapy

Interleukin-8 has long been recognized to have anti-inflammatory activity, which has been established in various models of infection, inflammation, and cancer. Several cell types express the receptor for the cytokine IL-8 and upon its recognition produce molecules that are active both locally and systemically. Many different types of cells, in particular monocytes, neutrophils, epithelial, fibroblast, endothelial, mesothelial, and tumor cells, secrete IL-8. Increased expression of IL-8 and/or its receptors has been characterized in many chronic inflammatory conditions, including psoriasis, ARDS, COPD, and RA as well as many cancers, and its upregulation often correlates with disease activity. IL-8 constitutes the CXC class of chemokines, a potent chemoattractant and activator of neutrophils and other immune cells. It is a proangiogenic cytokine that is overexpressed in many human cancers. Therefore, inhibiting the effects of IL-8 signaling may be a significant therapeutic intervention.