湖南地区幽门螺杆菌CagA基因3’端多态性与胃小二指肠疾病的关系

目的 探讨湖南地区幽门螺杆菌（Helifcobacter Hpylori）细胞毒素相关基因（CagA基因）3＇端可变区序列特征及其与胃十二指肠疾病的关系.方法 本地区有明显上消化道症状患者235例,其中慢性胃炎（CG）57例,胃溃疡（GU）62例,十二指肠溃疡（DU）70例,胃癌（GC）46例.于胃镜检查时用灭菌活检钳取胃窦组织1块,分离培养出H.pylori 89株,用PCR法对上述菌株的CagA基因扩增及测序,并通过生物信息学软件进行多重序列比对和相似性分析.结果 H.pylori培养阳性率为37.9%（89/235）,其中H.pylori CagA阳性者占91.7%（77/84）,GU组、DU组和GC组CagA阳性率高于CG组,其差异有统计学意义（P〈0.05）.77株H.pylori CagA基因3＇端均具有3个EPIYA重复序列,其中第2个EPIYA序列存在3种突变型,占18.2%（14/77）.H.pylori CagA基因3＇端序列特征以东亚型为主,占88.3%（68/77）,东亚型的CagA阳性菌株在GU组、DU组及GC组高于CG组（P〈0.05）.所有东亚型CagA阳性菌株CagA序列特征类似于Yamaoka报道的A型.结论 湖南地区H.pylori CagA阳性菌株以东亚型为主,均具有3个EPIYA重复序列,其中第2个序列存在3种突变型,其与消化性溃疡和胃癌发生有关.     

Multistep activation of the Helicobacter pylori effector CagA

Chronic infection with the Gram-negative bacterium Helicobacter pylori is a major risk factor for the development of gastric cancer. Accumulating evidence indicates that the H. pylori virulence determinant cytotoxin-associated gene A (CagA) has a key oncogenic role in the process. Certain biological activities of CagA require its tyrosine phosphorylation by host cell kinases. In this issue of the JCI, Mueller and colleagues report their detailed kinetic and functional analysis of CagA phosphorylation, which indicates that c-Src and c-Abl kinases sequentially phosphorylate CagA. Interestingly, the two phosphorylation events need not occur on the same CagA molecule but are both required for the biological effects of CagA. The results provide a clinically relevant example of how a successful bacterial pathogen has evolved to exploit the tightly coordinated, sequential activity of host cell kinases for virulence factor activation and induction of pathology.     

Interaction of CagA with Crk plays an important role in Helicobacter pylori-induced loss of gastric epithelial cell adhesion

CagA protein is a major virulence factor of Helicobacter pylori, which is delivered into gastric epithelial cells and elicits growth factor-like responses. Once within the cells, CagA is tyrosine phosphorylated by Src family kinases and targets host proteins required to induce the cell responses. We show that the phosphorylated CagA binds Crk adaptor proteins (Crk-II, Crk-I, and Crk-L) and that the interaction is important for the CagA-mediated host responses during H. pylori infection. H. pylori-induced scattering of gastric epithelial cells in culture was blocked by overexpression of dominant-negative Crk and by RNA interference-mediated knockdown of endogenous Crk. H. pylori infection of the gastric epithelium induced disruption of E-cadherin/catenin-containing adherens junctions, which was also dependent on CagA/Crk signaling. Furthermore, inhibition of the SoS1/H-Ras/Raf1, C3G/Rap1/B-Raf, or Dock180/Rac1/Wiskott-Aldrich syndrome protein family verprolin homologous protein pathway, all of which are involved downstream of Crk adaptors, greatly diminished the CagA-associated host responses. Thus, CagA targeting of Crk plays a central role in inducing the pleiotropic cell responses to H. pylori infection that cause several gastric diseases, including gastric cancer.     

Genetic diagnosis of H. pylori strains

Helicobacter pylori strains are divided into two broad families, type I and type II, based on whether or not they possess the cag pathogenicity island (cagPAI). It has been suggested that cagPAI is inherited by horizontal transfer from an unknown microorganism, and the genes of cag are thought to be encoded by a putative type IV secretory system. In addition, CagA may be delivered from attached H. pylori into the host crytoplasm by this system and is tyrosine phosphorylated in gastric epithelial cells. The phosphorylated CagA may play a crucial role in promoting the inflammatory responses of gastric mucosa. These findings suggest that type I H. pylori is a pathogenic H. pylori.     

Helicobacter pylori CagA protein can be tyrosine phosphorylated in gastric epithelial cells

Attachment of Helicobacter pylori to gastric epithelial cells induces various cellular responses, including the tyrosine phosphorylation of an unknown 145-kD protein and interleukin 8 production. Here we show that this 145-kD protein is the cagA product of H. pylori, an immunodominant, cytotoxin-associated antigen. Epithelial cells infected with various H. pylori clinical isolates resulted in generation of tyrosine-phosphorylated proteins ranging from 130 to 145 kD in size that were also induced in vitro by mixing host cell lysate with bacterial lysate. When epithelial cells were infected with [(35)S]methionine-labeled H. pylori, a radioactive 145-kD protein was detected in the immunoprecipitates with antiphosphotyrosine antibody or anti-CagA (cytotoxin-associated gene A) antibody. Consistently, the 145-kD protein recognized by the anti-CagA and antiphosphotyrosine antibodies was induced in epithelial cells after infection of wild-type H. pylori but not the cagA::Km mutant. Furthermore, the amino acid sequence of the phosphorylated 145-kD protein induced by H. pylori infection was identical to the H. pylori CagA sequence. These results reveal that the tyrosine-phosphorylated 145-kD protein is H. pylori CagA protein, which may be delivered from attached bacteria into the host cytoplasm. The identification of the tyrosine-phosphorylated protein will thus provide further insights into understanding the precise roles of CagA protein in H. pylori pathogenesis.     

消化道症状儿童白细胞介素-1基因簇多态性与幽门螺杆菌感染的研究

目的 分析探讨儿童白细胞介素-1(IL-1)基因簇多态性与幽门螺杆菌(H.pylori)感染间的相关性.方法 随机选取128例消化道疾病患儿的胃黏膜标本.IL-1B-31,IL-18-511 SNP位点多态性使用实时定量聚合酶链(real-time PCR) 双色荧光探针法检测,IL-IRN的可变重复序列使用传统PCR方法检测.Real-time PCR检测H.pylori的保守基因ure以判断H.pylori的感染,高毒力亚型基因vacA s1用Real-time PCR检测,用PCR扩增另-高毒力基因cagA羧基端EPIYA基因序列所在区,然后测序确定其亚型.结果 所研究的患儿中IL-1B-31T与IL-1B-511C完全连锁.未检测到H.pylori及其高毒力亚型感染与IL-1-511/-31SNP及IL-1RN基因多态性之间的相关性.结论 IL-1基因簇多态性不是广州地区儿童H.pylori感染的独立影响因素,它可能与其他因素共同影响着儿童H.pylori的感染.     

Relationship of Helicobacter pylori CagA(+) status to gastric juice vitamin C levels

BACKGROUND: To date it is not known whether gastric juice vitamin C levels are influenced by Helicobacter pylori CagA(+) strains. The aim of the present study, therefore, was to study the impact of H. pylori CagA status on gastric juice vitamin C levels. MATERIALS AND METHODS: We studied 30 H. pylori(+) patients, and the results were compared with 10 endoscopically and histologically normal H. pylori(-) subjects (control group) who were similar to the H. pylori(+) group in terms of age and sex. In all patients, gastric juice vitamin C levels were determined and the severity of gastritis was graded on a scale of 0 (absent) to 3 (severe). CagA was determined by immunoblotting the sera from patients against H. pylori antigens. RESULTS: Among 30 H. pylori(+) patients, 20 were CagA(+) and 10 CagA(-). In the entire group of H. pylori(+) patients, the median gastric juice vitamin C levels (mg L-1) were 16.35 (range 3.5-33.6) and were significantly lower (P < 0.001) than in the control group of H. pylori(-) patients [35.5 (23.1-50.2)]. In addition, in the entire group of H. pylori(+) patients there was a highly significant (P < 0.0001) inverse correlation between the gastritis activity score and the gastric juice vitamin C levels. In the group of H. pylori CagA(+) patients, the median levels of gastric juice vitamin C were 13.8 (3.5-31.2) and were significantly lower than the corresponding levels in both the H. pylori CagA(-) group [24.8 (22-33.6), P < 0.01] and the H. pylori(-) control group [35.5 (23.1-50.2), P < 0.001], the last groups being similar. Furthermore, the gastritis activity median score in the H. pylori CagA(+) group [2 (1-3)] was significantly higher (P < 0.05) than in the H. pylori CagA(-) group [1 (1-2)]. CONCLUSION: These data indicate that infection with CagA(+) H. pylori strains significantly lowers the gastric juice vitamin C levels in comparison with CagA(-) H. pylori strains, which might have a significant impact on gastric carcinogenesis.     

Helicobacter pylori induces beta3GnT5 in human gastric cell lines, modulating expression of the SabA ligand sialyl-Lewis x

Chronic Helicobacter pylori infection is recognized as a cause of gastric cancer. H. pylori adhesion to gastric cells is mediated by bacterial adhesins such as sialic acid-binding adhesin (SabA), which binds the carbohydrate structure sialyl-Lewis x. Sialyl-Lewis x expression in the gastric epithelium is induced during persistent H. pylori infection, suggesting that H. pylori modulates host cell glycosylation patterns for enhanced adhesion. Here, we evaluate changes in the glycosylation-related gene expression profile of a human gastric carcinoma cell line following H. pylori infection. We observed that H. pylori significantly altered expression of 168 of the 1,031 human genes tested by microarray, and the extent of these alterations was associated with the pathogenicity of the H. pylori strain. A highly pathogenic strain altered expression of several genes involved in glycan biosynthesis, in particular that encoding beta3 GlcNAc T5 (beta3GnT5), a GlcNAc transferase essential for the biosynthesis of Lewis antigens. beta3GnT5 induction was specific to infection with highly pathogenic strains of H. pylori carrying a cluster of genes known as the cag pathogenicity island, and was dependent on CagA and CagE. Further, beta3GnT5 overexpression in human gastric carcinoma cell lines led to increased sialyl-Lewis x expression and H. pylori adhesion. This study identifies what we believe to be a novel mechanism by which H. pylori modulates the biosynthesis of the SabA ligand in gastric cells, thereby strengthening the epithelial attachment necessary to achieve successful colonization.     

幽门螺杆菌感染及其毒力因子和胃十二指肠疾病关系的研究

目的 探讨幽门螺杆菌（Hp)感染病人中Hp细胞毒相关蛋白（CagA)、细胞空泡毒素（VacA)抗体在胃十二指肠疾病的比例，并评估不同类型幽门螺杆菌感染对胃窦粘膜炎症程度的影响。方法 应用免疫印迹法测定Hp感染者病人体内的CagA、VacA抗体。结果 73％的Hp感染者病人中出现CagA抗体，61％Hp感染者病人中出现VacA抗体。CagA抗体和VacA抗体在各疾病之间差异无显著性（P＞0．05）。在胃溃疡、十二指肠溃疡和复合性溃疡三类病人中，具CagA和VacA双阳性的比例较CagA和VacA双阴性的比例差异有显著性（P＜0．05）。胃窦萎缩病变在CagA和VacA双阳性的病人中比CagA和VacA双阴性的病人严重（P＜0．05）。结论 具有高毒力因子（CagA和VacA)的Hp是胃肠疾病病人感染的常见菌株，具有CagA和VacA的Hp可能在诱导胃粘膜发展到萎缩病变过程中起重要作用。但不能作为特异性指标来判断胃十二指肠疾病。     

Association of CagA-positive infection with Helicobacter pylori antibodies of IgA class

cagA gene, the best known virulence factor of Helicobacter pylori, codes for an immunodominant CagA protein. In this study, CagA antibodies of the IgG class were measured by immunoblot or enzyme immunoassay in subjects with positive H. pylori serology, and the presence of CagA antibodies was compared with that of H. pylori antibodies of IgA and IgG classes. Serum samples were available for a total of 1,481 subjects, including gastroscopied patients with biopsy-verified H. pylori infection, smoking men with a normal or low serum pepsinogen I level indicating atrophic corpus gastritis, and subjects who later developed gastric cancer and their matched controls. CagA antibodies were significantly more prevalent among individuals with elevated H. pylori antibody titres of the IgA class than in those with IgG antibodies only, with the exception of a small subgroup of individuals who later developed gastric cancer. CagA-positive H. pylori strains seem to induce an immune response with a markedly higher frequency of IgA than what is found in inflammation caused by CagA-negative strains. The presence of serum IgA antibodies to H. pylori seems to indicate a higher risk for CagA-positive H. pylori infection and possibly more severe late sequelae of the disease.     

儿童胃黏膜白细胞介素mRNA水平与幽门螺旋杆菌感染的研究

目的分析儿童胃黏膜白细胞介素(IL-1β)水平与幽门螺旋杆菌(H.pylori)及其高毒力亚型感染间的相关性。方法实时定量聚合酶链(real-time PCR)检测H.pylori的保守基因ure以判断H.pylori的感染,高毒力亚型基因vacA s1用real-time PCR检测,用PCR扩增另一高毒力基因cagA羧基端EPIYA基序所在区,然后测序确定其亚型。IL-1βmRNA使用PCR-荧光探针法检测,比较循环CT法分析。结果患儿中无论是低毒力还是高毒力的H.pylori感染都与胃黏膜IL-1βmRNA水平无显著相关性。结论 H.pylori对儿童胃黏膜IL-1β表达的影响作用并不明显,可能还有其他一些环境、遗传因素如IL-1基因簇多态性与H.pylori共同作用调节胃黏膜IL-1β的表达。     

Frequencies of serum antibodies to Helicobacter pylori CagA and VacA in a Turkish population with various gastroduodenal diseases

Infection with Helicobacter pylori (H. pylori) strains secreting cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) proteins is associated with more severe gastroduodenal pathologies. However, this association varies among geographical regions and ethnic groups. We investigated the frequencies of antibodies to CagA and VacA proteins in 131 H. pylori-infected dyspeptic patients [40 duodenal ulcer (DU), 19 gastric ulcer (GU), 28 gastric cancer (GC), and 44 non-ulcer dyspepsia (NUD)] across 30 H. pylori-infected and endoscopically normal asymptomatic subjects (AS). Anti-CagA and anti-VacA antibodies were detected by Western blotting. The positivity rates of anti-CagA and anti-VacA antibodies were higher in patients with DU (92.5 and 75%), GU (89.5 and 84.2%) and GC (96.4 and 85.7%) than patients with NUD (70.5 and 50%) and AS (50 and 23.3%) (p < 0.05). CagA+ VacA+ phenotype was more frequent in patients with DU, GU and GC than patients with NUD and AS (75, 84.2, 85.7 vs. 47.7 and 20%, respectively) (p < 0.01). Our results showed that there is a significantly positive association between the presence of anti-CagA and anti-VacA antibodies and DU, GU and GC in our region.     

Peculiarities of relationship between atrophic gastritis and stomach cancer in the population of Eastern Siberia

The authors studied the prevalence of atrophic gastritis, H.pylori strains carrying the CagA gene, seeding and apoptosis indices of gastric mucosa in indigenous and newcomer residents of Evenkia. A total of 136 Evenks and 159 newcomers were examined using fibrogastroscopy and biopsy of antral gastric mucosa. Morphological study included light microscopy of hematoxylin and eosin-stained biopsies and their analysis using a visual-analog scale to reveal signs of inflammation, apoptosis, intestinal metaplasia and the degree of insemination by P. pylori. Urease and morphological tests were used to identify H. pylori and the TUNEL technique (Mebstain Apoptosis kit direct, France) to determine apoptosis index; serum anti-Helicobacter and CagA antibodies were detected by an immunoenzyme assay in 22 Evenks and 24 newcomers with chronic H. pylori-associated gastritis. The prevalence of atrophic gastritis in these groups was estimated at 13.2 and 23.9% respectively, seeding density 45.37 +/- 2.01 and 214 +/- 8.75 (p < 0.001). H. pylori strains carrying the CagA gene were identified in 59.6 and 43.6% of the newcomers and Evenks (p = 0.01), total apoptosis index in greater curvature mucosa was 4.99 +/- 0.23 and 3.19 +/- 0.28 (p < 0.01) respectively. These ethnic difference in the prevalence of atrophic gastritis appear to be attributable to different intensity of apoptosis in greater curvature mucosa.     

Helicobacter pylori-induced apoptosis in T cells is mediated by the mitochondrial pathway independent of death receptors

BACKGROUND: Chronic infection with Helicobacter pylori is related to the pathogenesis of the noncardia carcinoma of the stomach. In this study we investigated the mechanisms of H. pylori-induced apoptosis in T lymphocytes, which could explain a mechanism of immune evasion facilitating chronic inflammation of the mucosa and gastric carcinogenesis. MATERIALS AND METHODS: The supernatant of H. pylori culture was used to study the mechanism of apoptosis induction in human leukaemia T cell lines Jurkat and CEM and in primary T cells. The cytotoxin associated gene A (CagA) and vacuolating cytotoxin A (Vac A) positive bacterial strain H. pylori 60190 (CagA(+), VacA(+)) and as a control the less toxic H. pylori strain Tx30a (CagA(-), VacA(-)) were used to produce the supernatant. Cell death was determined by DNA fragmentation and protein expression by Western blot. RESULTS: H. pylori 60190-induced apoptosis was neither blocked by inhibition of the death ligands TRAIL (TNF-related apoptosis-inducing ligand), CD95L/FasL and TNF-alpha (tumour necrosis factor-a) in wild type Jurkat cells nor in FADD(def) (Fas-associated death domain protein) and caspase-8(def) subclones of the Jurkat cell line. Yet, the pancaspase inhibitor zVAD-fmk could inhibit up to 90% of H. pylori-induced apoptosis. Stable transfection of Jurkat wild type cells with Bcl-x(L and) Bcl-2 resulted in marked reduction of H. pylori-induced apoptosis, showing that the mitochondrial pathway is the key regulator. This is supported by the finding that surviving primary human lymphocytes upregulate Bcl-2 when exposed to H. pylori supernatant. CONCLUSIONS: H. pylori-induced apoptosis of T cells is mediated by the mitochondrial pathway and could create a local environment that facilitates life-long infection by immune evasion.     

Virulent strains of Helicobacter pylori demonstrate delayed phagocytosis and stimulate homotypic phagosome fusion in macrophages

Helicobacter pylori colonizes the gastric epithelium of approximately 50% of the world's population and plays a causative role in the development of gastric and duodenal ulcers. H. pylori is phagocytosed by mononuclear phagocytes, but the internalized bacteria are not killed and the reasons for this host defense defect are unclear. We now show using immunofluorescence and electron microscopy that H. pylori employs an unusual mechanism to avoid phagocytic killing: delayed entry followed by homotypic phagosome fusion. Unopsonized type I H. pylori bound readily to macrophages and were internalized into actin-rich phagosomes after a lag of approximately 4 min. Although early (10 min) phagosomes contained single bacilli, H. pylori phagosomes coalesced over the next approximately 2 h. The resulting "megasomes" contained multiple viable organisms and were stable for 24 h. Phagosome-phagosome fusion required bacterial protein synthesis and intact host microtubules, and both chloramphenicol and nocodazole increased killing of intracellular H. pylori. Type II strains of H. pylori are less virulent and lack the cag pathogenicity island. In contrast to type I strains, type II H. pylori were rapidly ingested and killed by macrophages and did not stimulate megasome formation. Collectively, our data suggest that megasome formation is an important feature of H. pylori pathogenesis.     

Impact of CagA status on serum gastrin and pepsinogen I and II concentrations in Japanese children with Helicobacter pylori infection

The study aimed to determine the association between cytotoxin-associated gene product (CagA), serum gastrin and pepsinogen levels in Japanese children infected with Helicobacter pylori. Three hundred children were enrolled in the study. H. pylori infection was assessed using an enzyme-linked immunosorbent assay, and CagA status was assessed using immunoblotting. Serum gastrin and pepsinogen concentrations were measured by radioimmunoassay. H. pylori seroprevalence was 12.3% (37/300) and CagA status was identified in 28/37 H. pylori-seropositive children (75.7%). Serum pepsinogen I and II levels were significantly higher in CagA-seropositive than CagA-seronegative children with H. pylori infection. There was no significant relationship between CagA seropositivity and serum gastrin levels. In conclusion, CagA status has a significant impact on serum pepsinogen levels, possibly through enhanced gastric mucosal inflammation.     

Western blotting of total lysate of Helicobacter pylori in cases of atrophic body gastritis

BACKGROUND: Atrophic body gastritis is considered the first important step in the histogenesis of gastric carcinoma, a multistep process starting from chronic gastritis and progressing through chronic atrophic gastritis, intestinal metaplasia, and dysplasia. Helicobacter pylori is involved in the induction of atrophic body gastritis, but documentation of H. pylori infection is difficult because of the progressive disappearance of the bacterium. Our study aimed to detect past H. pylori infection in patients with atrophic body gastritis. METHODS: We used Western blot analyses of whole bacterial protein lysate of 2 different strains to probe sera from 143 patients. All sera were analyzed by ELISA (Bio-Rad), and results of gastric histology were available for all patients. RESULTS: Among 111 patient sera previously classified as negative for H. pylori infection by ELISA, 106 (95.5%) were positive when assayed by immunoblotting. CONCLUSIONS: Commercial diagnostic reagent sets may fail to detect H. pylori infection. Western blotting of whole bacterial protein extracts could provide the basis of a noninvasive serology tool able to assess previous infection with H. pylori in patients with atrophic body gastritis.     

Peculiarities of relationship between atrophic gastritis and stomach cancer in the population of East Siberia

The authors studied the relationship between atrophic gastritis and gastric cancer in Europeoid and Mongoloid populations of East Siberia. Screening for atrophic gastritis was carried out in parallel in Evenkia, Khakassia, and Tyva. 1492 Europeoids, 533 Khakasses, 493 Evenks, and 414 Tuvinians were examined by oesogastroduodenoscopy with simultaneous biopsy sampling. Morphological studies of gastric mucosa were performed by light microscopy of hematoxylin/eosin stained samples with evaluation of results based on the visual analogous scale. H.pylori was identified in Giemsa stain preparations. Immunoenzyme assay was used to detect IgG and IgG of H.pylori CagA. Gastric cancer morbidity was estimated using materials of local oncological dispensaries and autopsy data. The prevalence of antral atrophic gastritis was 25.8% in Europeoids, 15.2% in Khakasses, 14% in Evenks, and 25.8% in Tuvinians. The incidence of gastric cancer was 33.2 in Europeoids, 20.2 in Khakasses, and 50.7in Tuvinians per 100,000. The occurrence of H.pylori was similar in all these populations (roughly 90%). CagA strains were identified in 61.2% Europeoids, in 44% Khakasses, in 36.44% Evenks, and in 60% Tuvinians. The study revealed ethnic differences in the association between gastritis cancer and H.pylori CagA-related gastritis among populations of different regions of East Siberia.     

Helicobacter pylori upregulates expression of epidermal growth factor-related peptides, but inhibits their proliferative effect in MKN 28 gastric mucosal cells.

Acute exposure to Helicobacter pylori causes cell damage and impairs the processes of cell migration and proliferation in cultured gastric mucosal cells in vitro. EGF-related growth factors play a major role in protecting gastric mucosa against injury, and are involved in the process of gastric mucosal healing. We therefore studied the acute effect of H. pylori on expression of EGF-related growth factors and the proliferative response to these factors in gastric mucosal cells (MKN 28) derived from gastric adenocarcinoma. Exposure of MKN 28 cells to H. pylori suspensions or broth culture filtrates upregulated mRNA expression of amphiregulin (AR) and heparin-binding EGF-like growth factor (HB-EGF), but not TGFalpha. This effect was specifically related to H. pylori since it was not observed with E. coli, and was independent of VacA, CagA, PicA, PicB, or ammonia. Moreover, H. pylori broth culture filtrates stimulated extracellular release of AR and HB-EGF protein by MKN 28 cells. AR and HB-EGF dose-dependently and significantly stimulated proliferation of MKN 28 cells in the absence of H. pylori filtrate, but had no effect in the presence of H. pylori broth culture filtrates. Inhibition of AR- or HB-EGF- induced stimulation of cell growth was not mediated by downregulation of the EGF receptor since EGF receptor protein levels, EGF binding affinity, number of specific binding sites for EGF, or HB-EGF- or AR-dependent tyrosine phosphorylation of the EGF receptor were not significantly altered by incubation with H. pylori broth culture filtrates. Increased expression of AR and HB-EGF were mediated by an H. pylori factor > 12 kD in size, whereas antiproliferative effects were mediated by both VacA and a factor < 12 kD in size. We conclude that H. pylori increases mucosal generation of EGF-related peptides, but in this acute experimental model, this event is not able to counteract the inhibitory effect of H. pylori on cell growth. The inhibitory effect of H. pylori on the reparative events mediated by EGF-related growth factors might play a role in the pathogenesis of H. pylori-induced gastroduodenal injury.