Distinct Mechanism of Helicobacter pylori-mediated NF-κB Activation between Gastric Cancer Cells and Monocytic Cells

Maeda, Shin; Akanuma, Masao; Mitsuno, Yuzo; Hirata, Yoshihiro; Ogura, Keiji; Yoshida, Haruhiko; Shiratori, Yasushi; Omata, Masao

doi:10.1074/jbc.m105381200

Cited by 183 publications

(152 citation statements)

References 51 publications

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“…5B). Consistent with this finding, H. pylori has been shown to induce NF-B activation in mice peritoneal macrophages and in the human monocytic cell line, THP-1 (48). Thus, further studies are warranted to identify the receptor(s) for H. pylori HSP60 on macrophages that leads to NF-B activation but that signal(s) through a pathway independent of TLR-2, TLR-4, and MyD88.…”

Section: Discussionsupporting

confidence: 57%

Helicobacter pylori Heat Shock Protein 60 Mediates Interleukin-6 Production by Macrophages via a Toll-like Receptor (TLR)-2-, TLR-4-, and Myeloid Differentiation Factor 88-independent Mechanism

Gobert

Bambou

Werts

et al. 2004

Journal of Biological Chemistry

154

105

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Helicobacter pylori has been reported to induce interleukin-6 (IL-6) production in monocytes/macrophages and in chronically inflamed gastric tissues. The mechanism by which H. pylori induces IL-6 production in macrophages, however, has not been investigated. To identify the H. pylori factor responsible for this activity, we fractionated soluble proteins from H. pylori strain 26695 by ion exchange and size exclusion chromatography and screened the fractions for IL-6-inducing activity on RAW 264.7 macrophages. A single protein was purified and identified by mass spectrometry as H. pylori heat shock protein 60 (HSP60). Consistent with the observed IL-6-inducing activity of H. pylori HSP60, soluble protein extracts of H. pylori 26695 and SS1 strains that were depleted of this protein by affinity chromatography had dramatically reduced IL-6-inducing activities. The immunopurified HSP60 stimulated IL-6 production in macrophages. When stimulated with H. pylori HSP60 or intact bacteria, peritoneal macrophages from mice deficient in Toll-like receptor (TLR)-2, TLR-4, TLR-2/TLR-4, and myeloid differentiation factor 88 produced the same amount of IL-6 than macrophages from wildtype mice, demonstrating the independence of H. pylori HSP60 responses from these signaling molecules. H. pylori HSP60-induced IL-6 mRNA expression, and NF-B activation in RAW 264.7 cells was abrogated in the presence of MG-132, a proteasome inhibitor. In contrast, inhibitors of protein kinase A or C, mitogen-activated protein kinase kinase, and phosphoinositide 3-kinase had no effect on IL-6 mRNA levels. This study demonstrates the induction of innate immune responses by H. pylori HSP60, thereby implicating this highly conserved protein in the pathophysiology of chronic gastritis.

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Section: Discussionsupporting

confidence: 57%

Helicobacter pylori Heat Shock Protein 60 Mediates Interleukin-6 Production by Macrophages via a Toll-like Receptor (TLR)-2-, TLR-4-, and Myeloid Differentiation Factor 88-independent Mechanism

Gobert

Bambou

Werts

et al. 2004

Journal of Biological Chemistry

154

105

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“…These data are in agreement with previous in vitro studies using gastric epithelial gastric cell lines 15 and monocytic cell lines. 36 Shibata et al also performed immunohistochemistry and reported that IκB phosphorylation levels were similar between cagE mutant-infected gerbils and uninfected gerbils 20 ; however, the source of immunostaining cells was unclear in their study.…”

Section: Discussionmentioning

confidence: 94%

Pattern of Transcription Factor Activation in Helicobacter pylori–Infected Mongolian Gerbils

Kudo

Lü

et al. 2007

Gastroenterology

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Background & Aims-Helicobacter pylori interact with epithelial cells resulting in activation of cellular signaling pathways leading to an inflammatory response. The pattern and timing of transcription factor activation in H pylori-infected gastric mucosa remain unclear. We investigated the roles of transcription factors in the gastric mucosa of H pylori-infected gerbils over the course of the infection.

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“…In particular, the pluripotent pro-inflammatory cytokine IL-1b has a central role in the pathogenesis of Helicobacter pylori-induced mucosal inflammation (Guiraldes et al, 2001;Maeda et al, 2001;Straubinger et al, 2003). IL-1b gene expression and protein production are increased in H. pylori infection and reduced with successful eradication (Wang et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…In addition to its potent chemotactic activity, it can induce proliferation and migration of keratinocytes, endothelial cells, and melanoma cells (Rennekampff et al, 2000;Singh and Varney, 2000;Heidemann et al, 2003). IL-8 is expressed in many different cell types, including monocytes and macrophages, endothelial cells, keratinocytes, mesangial cells, and several human tumor cell lines (Schwarz et al, 1997;Klezovitch et al, 2001;Maeda et al, 2001). Although constitutive production of IL-8 appears to be infrequent in most cell types examined, its expression can be induced in many cell types by specific stimuli such as granulocyte colony-stimulating factor, lipopolysaccharide (LPS), phorbol 12-myristate 13-acetate, viruses, and doublestranded RNA (Kasahara et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Interleukin-1β stimulates IL-8 expression through MAP kinase and ROS signaling in human gastric carcinoma cells

et al. 2004

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Recent studies have suggested that the expression of interleukin-8 (IL-8) directly correlates with the vascularity of human gastric carcinomas. In this study, the effect of IL-1b on IL-8 expression in human gastric cancer TMK-1 cells and the underlying signal transduction pathways were investigated. IL-1b induced the IL-8 expression in a time-and concentration-dependent manner. IL-1b induced the activation of extracellular signalregulated kinases-1/2 and P38 mitogen-activated protein kinase (MAPK), but not the activation of c-jun aminoterminal kinse and Akt. Specific inhibitors of MEK-1 (PD980590) and P38 MAPK (SB203580) were found to suppress the IL-8 expression and the IL-8 promoter activity. Expression of vectors encoding a mutated-type MEK-1 and P38 MAPK resulted in decrease in the IL-8 promoter activity. IL-1b also induced the production of reactive oxygen species (ROS). N-acetyl cysteine (NAC) prevented the IL-1b-induced ROS production and IL-8 expression. In addition, exogenous H 2 O 2 could induce the IL-8 expression. Deletional and site-directed mutagenesis studies on the IL-8 promoter revealed that activator protein-1 (AP-1) and nuclear factor (NF)-jB sites were required for the IL-1b-induced IL-8 transcription. Electrophoretic mobility shift assay confirmed that IL-1b increased the DNA-binding activity of AP-1 and NF-jB. Inhibitor (PD980590, SB203580) and ROS scavenger (NAC) studies revealed that the upstream signalings for the transcription factors AP-1 and NF-jB were MAPK and ROS, respectively. Conditioned media from the TMK-1 cells pretreated with IL-1b could remarkably stimulate the in vitro growth of HUVEC and this effect was partially abrogated by IL-8-neutralizing antibodies. The above results suggest that MAPK-AP-1 and ROS-NF-jB signaling pathways are involved in the IL-1b-induced IL-8 expression and that these paracrine signaling pathways induce endothelial cell proliferation.

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Distinct Mechanism of Helicobacter pylori-mediated NF-κB Activation between Gastric Cancer Cells and Monocytic Cells

Abstract: NF-B is a critical regulator of genes involved in in-

Cited by 183 publications

References 51 publications

Helicobacter pylori Heat Shock Protein 60 Mediates Interleukin-6 Production by Macrophages via a Toll-like Receptor (TLR)-2-, TLR-4-, and Myeloid Differentiation Factor 88-independent Mechanism

Helicobacter pylori Heat Shock Protein 60 Mediates Interleukin-6 Production by Macrophages via a Toll-like Receptor (TLR)-2-, TLR-4-, and Myeloid Differentiation Factor 88-independent Mechanism

Pattern of Transcription Factor Activation in Helicobacter pylori–Infected Mongolian Gerbils

Interleukin-1β stimulates IL-8 expression through MAP kinase and ROS signaling in human gastric carcinoma cells

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