The Role of Heat Shock Protein 60 (HSP60) of Helicobacter pylori in Adhesion of H. pylori to Human Gastric Epithelial Cell

The role of chronic infections in causing coronary artery disease (CAD) has been investigated for the past several years. Among them, the role of Helicobacter pylori has stimulated keen interest. Though initial results were conflicting, there are growing data to support the role of H. pylori in CAD. The main mechanism of endothelial damage is hypothesized to be through molecular mimicry involving heat shock proteins. This study was designed to determine the prevalence of H.pylori and cytotoxin associated gene A (cagA) positive H.pylori infection in patients undergoing coronary artery bypass grafting (CABG) and the potential role of anti-H. pylori specific heat shock protein-60 (Hp-HSP-60) antibody response in these patients, for cardiac events. One hundred patients undergoing CABG and 100 controls were studied. The H.pylori infection and cagA status were determined serologically by enzyme-linked immunosorbent assay (ELISA). Hp-HSP-60 Immunoglobulin G (IgG) antibodies were estimated by using an in house ELISA. Although there was no difference in the prevalence of H.pylori infection in patients and controls (74% vs 70%), 58% of patients were infected with cagA positive H.pylori compared to 36% of controls (P=0.002). Mean systemic levels of Hp-HSP-60 IgG were also higher in patients than in controls (27.9 vs 18.7, P=0.0001). These antibody levels were also significantly higher in H.pylori positive patients (P=0.0001). There was a strong correlation between Hp-HSP-60 antibody levels and occurrence of myocardial infarction (P=0.003). CagA positive H.pylori infection may be associated with the development of CAD. High levels of Hp-HSP-60 antibodies may constitute a marker and/or concomitant pathogenic factor of the disease.

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A Virulence Factor of Helicobacter pylori: Role of Heat Shock Protein in Mucosal Inflammation After H. pylori Infection

Journal of Clinical Gastroenterology ◽

10.1097/00004836-199800001-00007 ◽

1998 ◽

Vol 27 ◽

pp. S35-S39 ◽

Cited By ~ 29

Author(s):

Shigeru Kamiya ◽

Hiroyuki Yamaguchi ◽

Takako Osaki ◽

Haruhiko Taguchi

Keyword(s):

Helicobacter Pylori ◽

Heat Shock ◽

Heat Shock Protein ◽

Virulence Factor ◽

Mucosal Inflammation ◽

H Pylori

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Heat-shock protein 60 homologue of Helicobacter pylori is associated with adhesion of H. pylori to human gastric epithelial cells

Journal of Medical Microbiology ◽

10.1099/00222615-46-10-825 ◽

1997 ◽

Vol 46 (10) ◽

pp. 825-831 ◽

Cited By ~ 42

Author(s):

H. YAMAGUCHI ◽

T. OSAKI ◽

N. KURIHARA ◽

H. TAGUCHI ◽

T. HANAWA ◽

...

Keyword(s):

Helicobacter Pylori ◽

Heat Shock ◽

Epithelial Cells ◽

Heat Shock Protein ◽

Heat Shock Protein 60 ◽

Gastric Epithelial Cells ◽

H Pylori

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Helicobacter pylori heat-shock protein 60 induces interleukin-8 via a Toll-like receptor (TLR)2 and mitogen-activated protein (MAP) kinase pathway in human monocytes

Journal of Medical Microbiology ◽

10.1099/jmm.0.46882-0 ◽

2007 ◽

Vol 56 (2) ◽

pp. 154-164 ◽

Cited By ~ 73

Author(s):

Ying Zhao ◽

Kenji Yokota ◽

Kiyoshi Ayada ◽

Yumiko Yamamoto ◽

Tomayuki Okada ◽

...

Keyword(s):

Helicobacter Pylori ◽

Heat Shock ◽

Heat Shock Protein ◽

P38 Mapk ◽

Heat Shock Protein 60 ◽

Human Monocytes ◽

Toll Like Receptor ◽

Mapk Signalling ◽

Mitogen Activated Protein ◽

H Pylori

Previous reports have indicated that Helicobacter pylori heat-shock protein 60 (H. pylori-HSP60), as an immunodominant antigen, induces interleukin (IL)-8 production in human monocytes. The exact mechanism by which H. pylori-HSP60 induces IL-8 production in monocytes has not been fully elucidated. In the present study, the downstream pathway by which H. pylori-HSP60 induces IL-8 secretion in human monocytic cell lines was investigated. Intact H. pylori, heat-killed H. pylori and H. pylori recombinant HSP60 (rHpHSP60) all induced the secretion of IL-8 and the activation of mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) and p38, but not c-Jun N-terminal kinase (JNK), up to 24 h in NOMO1 cells. The specific inhibitors PD98059 and U0126 (for ERK1/2 signalling) and SB203580 (for p38 MAPK signalling) down-regulated IL-8 secretion from rHpHSP60-treated NOMO1 cells. An anti-Toll-like receptor (TLR)2 antibody or TLR2 small interfering RNA (siRNA) partially inhibited the secretion of IL-8, and anti-TLR2 antibody also suppressed activation of ERK and p38 MAPK in rHpHSP60-treated NOMO1 cells. These reactions were associated with nuclear factor-κB (NF-κB)-mediated transcriptional activation, since U0126, SB203580 and the anti-TLR2 antibody decreased NF-κB activation. Taken together, the results suggest that ERK and p38 MAPK signalling linked to the TLR2 recognition receptor in human monocytes may be an important pathway in H. pylori-HSP60-induced IL-8 secretion.

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Immune Response against a Cross-Reactive Epitope on the Heat Shock Protein 60 Homologue of Helicobacter pylori

Infection and Immunity ◽

10.1128/iai.68.6.3448-3454.2000 ◽

2000 ◽

Vol 68 (6) ◽

pp. 3448-3454 ◽

Cited By ~ 39

Author(s):

Hiroyuki Yamaguchi ◽

Takako Osaki ◽

Masanori Kai ◽

Haruhiko Taguchi ◽

Shigeru Kamiya

Keyword(s):

Escherichia Coli ◽

Immune Response ◽

Helicobacter Pylori ◽

Heat Shock ◽

Heat Shock Protein ◽

Enzyme Linked Immunosorbent Assay ◽

Heat Shock Protein 60 ◽

Epitope Region ◽

H Pylori ◽

Human Hsp60

ABSTRACT We previously established a monoclonal antibody (MAb), designated H9, which reacts with the heat shock protein 60 (HSP60) homologue ofHelicobacter pylori as well as with other bacterial and human HSP60s. To determine the importance of a cross-reactive epitope on H. pylori HSP60 in H. pyloriimmunopathogenesis, we performed (i) mapping of an epitope on H. pylori HSP60 recognized by the H9 MAb, (ii) analysis of immunoglobulin G responses of patients with or without H. pylori infection to its epitope region, and (iii) studies of the protective effect of immunization with its epitope region onH. pylori infection in mice. The epitope recognized by the H9 MAb was mapped to the sequence of amino acids 189 to 203 (VEGMQFDRGYLSPYF) on the H. pylori HSP60 molecule. It was confirmed that the synthesized peptide designated pH9 was recognized by the H9 MAb. Enzyme-linked immunosorbent assay analysis showed that patients with H. pylori infection (n = 349) had significantly lower titers of pH9 antibody than did uninfected patients (n = 200) (P < 0.001), but this was not the case with purified H. pylori HSP60 recombinant Escherichia coli GroEL, or recombinant human HSP60. In C57BL/6 mice immunized with the pH9 peptide with Freund's complete adjuvant (FCA), the number of H. pylori organisms colonizing the stomach was significantly lower than that in mice immunized with pCont plus FCA (P < 0.0001) or FCA only (P < 0.005). The results suggest that the immune response to the cross-reactive epitope (pH9 region) on H. pylori HSP60 is unique and might be associated with protection against H. pylori infection.

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Effect of Bacterial Flora on Postimmunization Gastritis following Oral Vaccination of Mice with Helicobacter pylori Heat Shock Protein 60

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.10.5.808-812.2003 ◽

2003 ◽

Vol 10 (5) ◽

pp. 808-812 ◽

Cited By ~ 17

Author(s):

Hiroyuki Yamaguchi ◽

Takako Osaki ◽

Haruhiko Taguchi ◽

Noriko Sato ◽

Atushi Toyoda ◽

...

Keyword(s):

Helicobacter Pylori ◽

Heat Shock ◽

Heat Shock Protein ◽

Bacterial Flora ◽

Heat Shock Protein 60 ◽

Protective Effects ◽

Oral Vaccination ◽

Vaccine Protection ◽

Specific Pathogen ◽

H Pylori

ABSTRACT In order to assess the efficacy of oral Helicobacter pylori heat shock protein 60 (HSP60) as a vaccine, protection against H. pylori infection in specific-pathogen-free (SPF) C57BL/6 and germfree (GF) IQI mice was examined. Prophylactic oral vaccination of these two strains of mice with either H. pylori HSP60 or Escherichia coli GroEL inhibited H. pylori colonization by 90 to 95% at 3 weeks postinfection (p.i.). However, these mice were only partially protected because bacterial loads increased in all animals at 10 weeks p.i. Anti-H. pylori HSP60 immunoglobulin G was detected in serum at 3 weeks p.i. in mice vaccinated with either H. pylori HSP60 or GroEL. Significant increases in the gastritis scores were observed only in SPF mice immunized with H. pylori HSP60. These results indicate that oral vaccination with H. pylori HSP60 has partial protective effects on subsequent H. pylori infection but also induces postimmunization gastritis. However, GF mice immunized with H. pylori HSP60 did not suffer from severe gastritis. Therefore, the presence of bacterial flora appears to contribute to the induction of postimmunization gastritis.

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Serum Antibodies to Helicobacter pylori and its Heat-Shock Protein 60 Correlate with the Response of Gastric Mucosa-Associated Lymphoid Tissue Lymphoma to Eradication of H. pylori

Helicobacter ◽

10.1111/j.1083-4389.2004.00225.x ◽

2004 ◽

Vol 9 (3) ◽

pp. 194-200 ◽

Cited By ~ 12

Author(s):

Ryuta Takenaka ◽

Kenji Yokota ◽

Motowo Mizuno ◽

Hiroyuki Okada ◽

Tatsuya Toyokawa ◽

...

Keyword(s):

Helicobacter Pylori ◽

Heat Shock ◽

Gastric Mucosa ◽

Heat Shock Protein ◽

Lymphoid Tissue ◽

Heat Shock Protein 60 ◽

Serum Antibodies ◽

H Pylori

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Effects ofHelicobacter pyloriand Heat Shock Protein 70 on the Proliferation of Human Gastric Epithelial Cells

Gastroenterology Research and Practice ◽

10.1155/2014/794342 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5 ◽

Cited By ~ 2

Author(s):

Liping Tao ◽

Hai Zou ◽

Zhimin Huang

Keyword(s):

Helicobacter Pylori ◽

Heat Shock ◽

Epithelial Cells ◽

Heat Shock Protein ◽

Mtt Assay ◽

Heat Shock Protein 70 ◽

Hsp70 Expression ◽

Gastric Epithelial Cells ◽

Ags Cells ◽

H Pylori

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

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