Analysis of interleukin-8 secretion induced by Helicobacter pylori from the gastric epithelial cell line MKN45: A mechanism independent of the intensity of cytotoxicity

Interleukin (IL)-8, a potent chemoattractant and activator of neutrophils, has been implicated to have a major role in the pathogenesis of gastric mucosal injury by Helicobacter pylori infection. We examined the relationship between cytotoxicity and IL-8 secretion induced by H. pylori. Furthermore, whether the vacuolating cytotoxin of H. pylori mediates IL-8 secretion from gastric epithelial cell lines was examined. Among the inflammatory cytokines, messages for IL-6, IL-8 and transforming growth factor-β₁ were produced by gastric cancer (MKN45) cells in response to exposure to the cytotoxic strain of H. pylori. MKN45 incubated with the viable cytotoxic strain of H. pylori. secreted IL-8. In contrast, the supernatant of neither the cytotoxic nor the non-cytotoxic strain induced IL-8 secretion. There was no correlation between IL-8 secretion and the intensity of cytotoxicity. In conclusion, these findings suggest that IL-8 secretion from MKN45 induced by H. pylori is mediated by factors other than cytotoxicity.     

Water extract of Helicobacter pylori stimulates interleukin-8 secretion by a human gastric epithelial cell line (JR-St) through protein tyrosine phosphorylation

BACKGROUND: Infection by Helicobacter pylori induces cytokine production in gastric mucosal cells. Production of interleukin-8 (IL-8) is known to be markedly increased and is believed to play an important role in gastric mucosal inflammation. The aim of this study was to elucidate the effects of soluble factors of H. pylori on IL-8 production in a gastric epithelial cell line, JR-St. METHODS: JR-St cells were cocultured with a H. pylori water extract, live H. pylori or culture medium supernatant for 24 h, then the IL-8 secreted into the culture medium was assayed. The effects of three different inhibitors; (i) an inhibitor of protein kinase C (PKC); (ii) an inhibitor of PKC and protein kinase A (PKA); and (iii) an inhibitor of protein tyrosine kinase (PTK) were also compared. Specific induction of IL-8 mRNA was also examined. RESULTS: Water extract of H. pylori increased IL-8 secretion 7.72-fold, more than the control. The increase was concentration dependent. Live bacteria, supernatant and water extract significantly stimulated IL-8 secretion. Addition of live bacteria increased IL-8 secretion most strongly, while the effect of water extract was small (22% that of live bacteria). Secretion was not inhibited by the PKC inhibitor staurosporine or the inhibitors of PKA and PKC H7. However, secretion was significantly reduced by the PTK inhibitor herbimycin in a dose-dependent manner. Furthermore, 24 h exposure to water extract increased IL-8 mRNA expression, suggesting water extract increased production of IL-8. CONCLUSIONS: Some soluble factors of H. pylori can stimulate IL-8 production by JR-St cells. Stimulation was not dependent on PKA or PKC but was, at least partially, dependent on protein tyrosine phosphorylation. This suggests that soluble factors of H. pylori can play an important role in mediating the inflammatory response of H. pylori gastritis.     

cag致病岛的差异及不同激酶抑制剂对幽门螺杆菌诱导胃上皮细胞IL-8分泌的影响

目的：分析中国临床分离的幽门螺杆菌的cag致病岛的差异和不同激酶抑制剂对幽门螺杆菌诱导中国人胃上皮细胞IL-8分泌的影响。方法：在体外分别用中国临床分离的cagA^ cagE^ 、cagA^ cagE^ 、cagA^ cagE^ 、cagA^ cagE^ 的幽门螺杆菌与中国人胃上皮细胞MGC-803共培养,IL-8分泌用ELISA进行检测,比较蛋白激酶A、C、G和蛋白酪氨酸激酶的抑制剂对幽门螺杆菌诱导胃上皮细胞IL-8分泌的影响。结果：cagA^ cagE^ 幽门螺杆菌显增加了胃上皮细胞IL-8的分泌,cagA^ cagE^ 、cagA^ cagE^ 幽门螺杆菌作用次之,而cagA^ cagE^ 幽门螺杆菌不能增加胃上皮细胞IL-8的分泌。蛋白激酶A、C、G的抑制剂不能阻断幽门螺杆菌增加胃上皮细胞IL-8的分泌,而蛋白酪氨酸激酶的抑制剂阻断了幽门螺杆菌增加胃上皮细胞IL-8的分泌。结论：cagA^ cagE^ 幽门螺杆菌显增加了胃上皮细胞IL-8的分泌并且依赖于蛋白酪氨酸激酶的活性。     

Mechanism for gastric cancer development by Helicobacter pylori infection

Helicobacter pylori (H. pylori) infection plays a crucial role in the development of gastric cancer. There are two major pathways for the development of gastric cancer by H. pylori infection: the indirect action of H. pylori on gastric epithelial cells through inflammation, and the direct action of the bacteria on epithelial cells through the induction of protein modulation and gene mutation. Both pathways work together to promote gastric carcinogenesis.     

Association between interleukin-1 gene polymorphisms and Helicobacter pylori infection in gastric carcinogenesis in a Chinese population

BACKGROUND AND AIM: Helicobacter pylori is a major cause of chronic gastritis and peptic ulcer disease and a definite carcinogen for gastric adenocarcinoma. However, the underlying pathogenic mechanisms are not fully understood. Interleukin-1 (IL-1) is a key cytokine involved in H. pylori-induced gastric inflammation. The present study aimed to determine polymorphisms of IL-1B and IL-1 receptor antagonist (IL-1RN) genes and their association with H. pylori infection and gastroduodenal diseases in Chinese patients. METHODS: Three hundred and ninety-nine patients with gastroduodenal diseases (129 chronic gastritis, 127 duodenal ulcer and 143 non-cardiac gastric cancer) and 264 healthy controls were genotyped for IL-1B-511 and IL-1RN gene polymorphisms by the PCR-RFLP method. H. pylori infection status was determined by a validated serological test. RESULTS: The frequency of IL-1B-511 T allele was significantly higher in H. pylori positive patients with non-cardiac gastric cancer than in both H. pylori negative patients with non-cardiac gastric cancer (60%vs 46%, P = 0.0342, OR = 1.666, 95% confidence interval [CI]: 1.045-2.656) and in healthy controls (60%vs 48%, P = 0.0071, OR = 1.665, 95%CI: 1.149-2.412). However, the polymorphism was not associated with chronic gastritis and duodenal ulcer. Multivariate logistic regression analyses identified that IL-1B-511 T/T carrier status was an independent risk factor for non-cardiac gastric cancer in the presence of H. pylori infection (adjusted OR = 3.01, 95%CI: 1.27-7.11, P = 0.01), and the frequency of IL-1B-511 T allele was an increased risk factor for developing gastric cancer (P = 0.03, adjusted OR = 2.29, 95%CI: 1.08-4.86). There was no association between IL-1RN gene polymorphisms and H. pylori infection and other gastroduodenal diseases. CONCLUSION: IL-1B-511 T allele is associated with H. pylori infection in non-cardiac gastric cancer in a Chinese population. The IL-1B-511 gene polymorphism appears to play an important role in gastric carcinogenesis in Chinese patients with H. pylori infection.     

Effects of interleukin-8 and Helicobacter pylori on histamine release from isolated canine gastric mucosal mast cells

Background. In recent studies, the involvement of mast cells in the pathogenesis of Helicobacter pylori infection was suggested. In the present study, using isolated canine gastric mucosal mast cells, we undertook to elucidate the effects of interleukin-8 (IL-8) and H. pylori on histamine release from these cells. Methods. Enriched canine gastric mucosal mast cells (50% target cells) were incubated in Hanks medium with IL-8, or water extract or sonicate of H. pylori for 15 min at 37°C. The content of histamine in the supernatants and the cell pellets after centrifugation was assayed with a histamine radioimmunoassay (RIA) kit. Results. IL-8 (50 ng/ml) and concanavalin A (20 μg/ml) significantly increased histamine release from enriched gastric mucosal mast cells. Dose-dependent stimulation of histamine release by IL-8 (5–50 ng/ml) was also seen. Water extract and sonicate of H. pylori (10⁸ bacteria) increased histamine release from mast cells. A concentration-dependent stimulation of histamine release by water extract or sonicate was also seen. The maximal response of histamine release was seen at the highest concentration of the water extract or sonicate. Conclusions. The results indicated that IL-8 and H. pylori had stimulatory effects on histamine release from canine gastric mucosal mast cells. The results imply that IL-8 and soluble factors of H. pylori may accelerate inflammation of the gastric mucosa via histamine release from mast cells. Received: February 28, 2001 / Accepted: July 6, 2001     

Gastric mucosal cytokine levels in relation to host interleukin-1 polymorphisms and Helicobacter pylori cagA genotype

Objective The outcome of a Helicobacter pylori infection is related in part to interrelationships among H. pylori virulence factors and the H. pylori-induced mucosal response. The host inflammatory response is partly governed by polymorphisms in pro-inflammatory genes.

Material and methods Cytokine levels (interleukin (IL)-1β, IL-6 and IL-8) were examined in H. pylori-infected and uninfected normal-appearing mucosa from patients with non-ulcer dyspepsia (NUD), margins of gastric ulcers and cancer tissues. Cytokine levels were compared with cagA genotypes and host interleukin (IL)-1 polymorphisms.

Results The study comprised 168 Thai patients. All infected patients possessed anti-CagA antibody. Gastric mucosal IL-8 levels were significantly higher in H. pylori-positive cases than in -negative cases in all three tissue types (e.g. 1115 versus 217?pg/mg protein for NUD) (p<0.001). Normal-appearing but H. pylori-infected antral mucosa of patients with cagA type 1a strains had higher IL-8 levels than those with type 2a strains (2632 versus 1036 pg/mg protein) (p<0.005). IL-1B-511T/T carriers had higher antral mucosal IL-1β levels versus non-carriers (pg/mg protein) (T/T=221, T/C=178, C/C=70) (p=0.005). IL-1B-511T/T carriers also had higher IL-1β levels versus non-carriers in H. pylori-negative patients.

Conclusions It was found that both the host factors (IL-1 polymorphisms) and bacterial factors (cagA type 1a versus type 2a) influenced gastric mucosal cytokine levels. Future studies should concentrate on interactions among host factors (e.g. genetics and tissue responses) and bacterial and environmental factors.     

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

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 （HpyloriSS1-LPS）. METHODS： SGC-7901 cells were treated with HpyloriSS1-LPS in the presence or absence of pretreatment for 1 h with viable LBG or supernatant 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 TAKI, subsequently enhanced the activation of NF- κB and the phosphorylation of p38MAPK in a time- dependent 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 py/oriSS1-LPS induces IL-8 production 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.     

Enhanced mucosal expression of interleukin-6 mRNA but not of interleukin-8 mRNA at the margin of gastric ulcer in Helicobacter pylori-positive gastritis

To elucidate the role of interleukin (IL)-6 and IL-8 in the pathogenesis of gastric ulcer in Helicobacter pylori-positive gastritis, in situ hybridization using digoxigenin-labeled cDNA probes for both cytokines was performed. Immunogold silver staining was added to further improve the sensitivity of this non-radioactive hybridization. The biopsy specimens were taken from eight patients with active gastric ulcer before treatment, in all of whom H. pylori was positive. Macrophages (the putative producers of these cytokines) were determined by immunohistochemistry using anti-CD68 monoclonal antibodies (KP-1). IL-6 mRNA was most abundantly expressed in the epithelium and in the infiltrating cells in tissue adjacent to gastric ulcer. Quantitative analysis disclosed a significant increase in cells positive for IL-6 mRNA near the ulcer margin compared to cells in the surrounding tissue. In contrast, cells positive for IL-8 mRNA were observed in equal proportions and evenly in the epithelium and over the entire layer of the gastric mucosa regardless of the presence of gastric ulcer. The majority of infiltrating cells positive for both IL-6 and IL-8 mRNA were thought to be macrophages because of their morphologic features and their immunohistochemical reactivity to CD68. These findings strongly suggest that IL-6 is overexpressed at the margin of gastric ulcer in H. pylori-positive gastritis. Received Sept. 24, 1997; accepted Mar. 19, 1998     

幽门螺杆菌感染致动脉粥样硬化机制的研究

动脉粥样硬化是引起心脑血管疾病的主要病理基础.大量实验和临床研究证明幽门螺杆菌（H.pylori）感染在动脉粥样硬化的发展中起重要作用.本文就近年来有关H.pylori感染致动脉粥样硬化机制的文献作一概述.     

中国幽门螺杆菌胃上皮细胞白细胞介素-8的转录能力

目的探讨中国幽门螺杆菌(Hp)的空泡毒素基因(vacA)型及cag致病岛对胃上皮细胞白细胞介素-8(IL-8)转录的影响.方法以基因测序与Southern杂交法确定HpvacA基因型及cag致病岛状态;构建带有IL-8报告基因的人胃癌细胞系L5F11,用液体闪烁计数仪测定荧光素酶活性(IL-8转录),用HeLa细胞测定空泡毒素活性.结果所有cag致病岛完整菌株(15株)较野生型cag致病岛阴性菌株G50诱导荧光素酶活性[记数/分(cpm)]明显增强[(0.47±0.19)×106cpm比(0.13±0.02)×106cpm,P＜0.01];而cag致病岛部分丢失菌株(4株)荧光素酶活性与G50差异无显著性[(0.23±0.08)×106cpm比(0.13±0.02)×106cpm,P＞0.05];vacA基因s1/m1型菌株(5株)较s1/m2型菌株(14株)空泡毒素活性增强(P＜0.01),但二者诱导荧光素酶活性差异无显著性[(0.29±0.12)×106cpm比(0.53±0.41)×106cpm,P＞0.05].结论中国Hp诱导胃上皮细胞IL-8转录能力与cag致病岛状态密切相关,而与vacA基因型无明显关系.     

Effect of age and Helicobacter pylori infection on gastric acid secretion

BACKGROUND: Whether gastric acid secretion decreases with age is still controversial. With the discovery of Helicobacter pylori, the association of this bacterium with gastric acid secretion has also been discussed. The aim of this study was to investigate the relationship between gastric acid secretion, age and H. pylori infection. METHODS: The presence of H. pylori infection, the grade of fundic atrophic gastritis (FAG), and gastric acid secretion were investigated in 280 subjects without localized lesions in the upper gastrointestinal tract. Helicobacter pylori infection was confirmed by Giemsa and immunohistochemical staining, and FAG of biopsy specimens was graded on a scale of 0-4. RESULTS: Both basal and maximal acid output decreased with age in H. pylori-positive subjects, while they did not change with age in H. pylori-negative subjects. Gastric acid secretion decreased with the progression of FAG. An age-correlated decrease in gastric acid secretion in H. pylori-positive subjects depended on an increasing prevalence of FAG with age. CONCLUSIONS: In the population studied, advancing age had no influence on gastric acid secretion in H. pylori-negative subjects. Gastric acid secretion decreases with age in H. pylori-positive subjects because of the increasing prevalence of FAG with age.     

Hp感染胃粘膜IL 8及ICAM 1的免疫组化研究

目的检测Ｈｐ感染胃粘膜ＩＬ８和ＩＣＡＭ１的变化，探讨其在Ｈｐ相关性胃十二指肠疾病发病机制中的可能作用．方法内镜下采取胃窦粘膜活检标本．经尿素酶试验、Ｈｐ培养和ＷａｒｓｈｉｎｇＳｔａｒｒｙ染色确定有无Ｈｐ感染；恒冷箱胃粘膜切片（６μｍ），光镜下按Ｃａｒｉｃｋ标准作胃粘膜炎症分级，免疫组化染色检测胃粘膜ＩＬ８和ＩＣＡＭ１的表达．结果Ｈｐ＋胃粘膜炎症重于Ｈｐ－者，在慢性炎症基础上常常合并有活动性炎症；ＩＬ８和ＩＣＡＭ１表达在Ｈｐ＋胃粘膜分别为６６７％（８／１２）和６００％（９／１５），而Ｈｐ－者均为４００％（４／１０）；其表达部位主要位于胃间质单个核细胞和腺上皮细胞．结论Ｈｐ阳性胃粘膜ＩＬ８及ＩＣＡＭ１表达较高，提示Ｈｐ感染时ＩＬ８和ＩＣＡＭ１在胃粘膜局部大量中性粒细胞和淋巴细胞浸润中可能起重要作用．     

Association between Helicobacter pylori infection and the risk of gastric cancer in the Korean population: prospective case-controlled study

Background. Gastric cancer is still the most common malignant tumor in Koreans. Although many reports have supported the association of Helicobacter pylori infection and the development of gastric cancer, few studies have been adjusted by variable factors such as age, sex, education, and economic status. Furthermore, most results from areas with a high incidence of gastric cancer, such as China and Korea, have failed to document any relationship between H. pylori infection and gastric cancer. We conducted a prospective case-controlled study, with controls matched for and adjusted by age, sex, education, and economic status, to evaluate the causal relationship between H. pylori infection and gastric cancer in Korean people. Methods. From March 1997 to October 1998, 136 consecutive patients with gastric cancer, diagnosed by endoscopic histology, and 136 age- and sex-matched control subjects, confirmed to be free of gastric cancer by endoscopy during the same period, were enrolled in the study. The presence of H. pylori infection was determined by enzyme immunoassay (EIA) serology test. Results. Seventy-two of the 136 gastric cancer patients (53%) were positive for H. pylori infection and 54 of the 136 control subjects (40%) were positive for H. pylori infection. The odds ratio (OR), adjusted by variable risk factors, such as age, sex, education, and economic status, for gastric cancer in H. pylori-infected patients was 1.82 (95% confidence internal [CI], 1.10–3.00; P = 0.019). The age- and sex-matched OR by conditional logistic regression was 1.6 (95% CI, 1.01–2.53; P = 0.043). Conclusions. H. pylori infection may be one of the important risk factors for the development of gastric cancer in Korea, an area of high prevalence of H. pylori infection and a high incidence of gastric cancer. Received: September 27, 2000 / Accepted: May 25, 2001     

Development of gastric adenocarcinoma in Mongolian gerbils after long-term infection with Helicobacter pylori

BACKGROUND AND AIM: The experimental evidence that long-term colonization of Helicobacter pylori results in the development of gastric cancer in Mongolian gerbils has been reported only by two Japanese groups to date. This study aimed to investigate the carcinogenicity of H. pylori infection in a Mongolian gerbil model. METHODS: Thirty-six Mongolian gerbils (inner Mongolian origin) were divided into two groups (male to female ratio, 1:1) and orally inoculated with a standard H. pylori strain (ATCC43504) or H. pylori161 (isolated from a Chinese patient with gastric adenocarcinoma), respectively, once a week for 5 weeks. Another 10 control gerbils were given phosphate-buffered saline. The animals were killed 8, 20, 28 and 84 weeks after inoculation for bacterial and histological examination. RESULTS: Seven inoculated gerbils died at the week 42. Overall, H. pylori colonization was detected in 24 (83%) of the 29 available inoculated gerbils. The gastric lesions were aggravated gradually over time. At week 84, moderate to severe gastritis, characterized by diffuse infiltration of mononuclear cells and formation of multiple lymphoid follicles in mucosa and submucosa, and even the lymphoepithelial lesions, were observed. Epithelial hyperplasia were dominant in almost all gerbils. Four (24%) of the 17 animals had hyperplastic polyps. Intestinal metaplasia were rarely seen (in three gerbils). Well-differentiated gastric adenocarcinomas developed in three (18%) of the 17 gerbils after 84 weeks. Of the three gerbils, one female gerbil was infected with H. pylori161 and the others (one male and one female) were infected with ATCC43504. CONCLUSIONS: The present study reconfirms that H. pylori infection alone can induce gastric adenocarcinoma in Mongolian gerbils and suggests that different species of gerbil and both standard and clinically isolated H. pylori strains can be used for investigating the carcinogenesis of H. pylori. This is the first report of the development of gastric cancer in female gerbils, which highlights the importance of using both sexes to investigate the pathogenesis of H. pylori and whether host susceptibility is influenced by sex.     

Epidemiology of gastric cancer in relation to diet and Helicobacter pylori infection

Abstract Gastric cancer is the second most common fatal malignancy in the world. In China, gastric cancer is now the second most common malignancy, while in Hong Kong, the mortality rate ranked fourth among all cancers in 1995. Dietary factors in gastric carcinogenesis came mostly from case-control studies. N-Nitroso compounds from dietary sources such as preserved, smoked and salted foods were found to be associated with gastric cancer. ß-Carotene, selenium and α-tocopherol have been shown in an intervention study to be favourable in the reduction of stomach cancer mortality. Fruits and vegetables showed the most consistent results of inverse association with gastric cancer. Dietary salt intake in preserved or salted foods is also shown to be associated with gastric cancer. Tea drinking, especially green tea, has a protective effect against gastric cancer as shown in some studies. Prospective case-control studies of the association between Helicobacter pylori infection and the subsequent development of gastric cancer showed that the odds ratio ranged from 2.8 to 6.0. However, results of similar case-control studies in countries with a high frequency of gastric cancer are controversial. Infection with H. pylori leads to changes in the vitamin C content of gastric juice, reactive oxygen metabolites, epithelial cell proliferation and apoptosis. Recently, CagA-positive strains were found to be associated with gastric cancer and also duodenal ulcers. The exact role of H. pylori in gastric carcinogenesis is still under investigation. Large-scale intervention studies are underway to examine dietary supplementation, H. pylori infection and gastric cancer. Helicobacter pylori eradication for gastric cancer prevention is being conducted in China and other parts of the world. In high-risk areas, for example in China, a combination approach including H. pylori eradication and dietary supplementation may be necessary.     

Helicobacter pylori infection: mechanism of colonization and functional dyspepsia Reduced colonization of gastric mucosa by Helicobacter pylori in mice deficient in interleukin-10

BACKGROUND AND AIMS: Interleukin-10 (IL-10) is a potent anti-inflammatory and immunoregulatory cytokine. Mice deficient in IL-10 production (IL-10-/-mice) develop a spontaneous chronic enterocolitis, suggesting that IL-10 is an important regulator of the mucosal immune response in vivo. The objective of this study was to determine the role of endogenous IL-10 in the host defense against gastric colonization by Helicobacter pylori by using IL-10-deficient mice. METHODS: The IL-10-/-mice were inoculated intragastrically with a mouse-adapted H. pylori isolate (Sydney Strain 1). Gastric colonization by H. pylori (biopsy urease test and bacterial colony counts), serum levels of H. pylori-specific immunoglobulin (Ig) M, A, G, isotypes of IgG, and the gastric mucosal inflammatory scores were determined 6 weeks after inoculation. Results were compared with those obtained from H. pylori-infected control mice (IL-10+/-mice). RESULTS: The colonization of gastric mucosa by H. pylori was reduced approximately 100-fold (P < 0.0001) in IL-10-/-mice (log10 4.87 +/- 0.26CFU/g tissue) as compared to IL-10+/-mice (log10 6.64 +/- 0.22 CFU/g tissue). Furthermore, IL-10-/-mice infected with H. pylori had significantly higher H. pylori-specific IgA and IgG antibodies in serum (P < or = 0.01), and developed much more severe chronic active gastritis than infected IL-10+/-mice. The median scores of the infiltration of gastric mucosa by mononuclear cells and neutrophils were up to threefold higher in IL-10-/-mice than they were in IL-10+/-mice. CONCLUSION: Our studies suggest that endogenous IL-10 is an inhibitor of the protective immune response to H. pylori infection. Interleukin-10 participates in the downregulation of H. pylori-induced gastric inflammatory responses, which apparently confers a survival advantage to the organism promoting more effective colonization of gastric mucosa.     

Risk of gastric cancer in Helicobacter pylori infection in a 15-year follow-up

Objective: We investigated the risk of gastric cancer among men with Helicobacter pylori (H. pylori) infection or atrophic gastritis (AG) in a 15-year follow-up.

Materials and methods: Study population consists of 12,016 men aged 50–65 years at the beginning of the follow-up in 1994–1996. Serum levels of pepsinogen I (SPGI) and antibodies (IgG) to H. pylori (HpAb) were assayed from serums collected in 1994–1996. Incidence of gastric cancer in the study population was assessed in follow-up from 1994 to 2011 by data from the nationwide cancer registry. Based on SPGI and HpAb values, standardized incidence ratios (SIRs) of gastric cancer were calculated in three subgroups, that is, in those with a healthy stomach, those with H. pylori infection but without AG and those with AG. Risk ratios (RR) of gastric cancer were calculated using SIR of subgroups.

Results: During 15 years, seven gastric cancers appeared per 79,928 person years among men with healthy stomachs, 50 cancers per 92,533 person years in men with H. pylori infection but without AG, and 8 per 8658 person years in men with AG. Risk ratio (RR) of stomach cancer in men with H. pylori infection was 5.8 (95%CI: 2.7–15.3) compared to men with healthy stomachs, and 9.1 (95%CI: 2.9–30.0) in men with AG. There were no differences in cancer risk between cardia and distal stomach.

Conclusions: Risk of gastric cancer is low in men with healthy stomachs. It is significantly increased in those with H. pylori infection and more in those with AG.     

Role of serum factors in epithelial cell responses to Helicobacter pylori infection in vitro

BACKGROUND: Gastric epithelial cell lines have been utilized extensively as tools to define aspects of the interactions between Helicobacter pylori and host epithelial cells. Fetal calf serum (FCS) is employed as a growth stimulant, but it is unclear whether this agent may in itself alter host responses. METHODS: Two gastric epithelial cell lines were utilized to ascertain the effects of varying FCS concentration on cellular responses following H. pylori infection. Media containing 0%, 5% or 10% FCS was added to cell lines prior to infection with H. pylori of defined genotype. Cellular interleukin (IL)-8 production was measured as a marker of cellular response. Effects of altered FCS upon cell viability were also determined by trypan blue exclusion. RESULTS: Interleukin-8 production by AGS cells following H. pylori infection was not altered by variation of media FCS concentration. However, KATO-III cells produced greater amounts of IL-8 when media was FCS-free than at 5% or 10% FCS. Although cellular viability was not altered in AGS cells exposed to varied concentrations of FCS, viability was decreased in serum-free KATO-III cells, but not when cells were kept at 5% FCS. CONCLUSIONS: Serum-derived factors alter cellular responses to H. pylori infection in a cell-line-dependent manner and impaired cellular viability may relate to this effect. However, the mechanisms for these observations are unclear and further work is now required to determine the nature of these important interactions.