Overexpression of<i>Helicobacter pylori</i>VacA N-terminal fragment induces proinflammatory cytokine expression and apoptosis in human monocytic cell line through activation of NF-κB

Luo, Jingjing; Li, Cunyan; Liu, Sheng; Wen, Yongning; Tang, Shuangyang; Cai, Hengling; Zhang, Yan

doi:10.1139/cjm-2013-0021

Cited by 19 publications

(12 citation statements)

References 50 publications

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“…VacA plays several roles in cellular pathogenicity (Table 1), and it is considered a multifunctional toxin eliciting multiple effects on host cells like vacuolization and cell necrosis [56,57]. Numerous studies have also shown cell apoptosis induction by VagA through the mitochondrial pathway in gastric epithelial cells [58,59,60]. An additional apoptotic potential was elaborated in a study, which provided novel evidence that VacA triggers the endoplasmic reticulum stress response to activate autophagy and increased cellular death of AGS cells [61].…”

Section: Virulence Factors Associated With Gastric Epithelial Cellmentioning

confidence: 99%

Helicobacter pylori Virulence Factors Exploiting Gastric Colonization and its Pathogenicity

Ansari

Yamaoka

2019

Toxins

174

141

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Helicobacter pylori colonizes the gastric epithelial cells of at least half of the world’s population, and it is the strongest risk factor for developing gastric complications like chronic gastritis, ulcer diseases, and gastric cancer. To successfully colonize and establish a persistent infection, the bacteria must overcome harsh gastric conditions. H. pylori has a well-developed mechanism by which it can survive in a very acidic niche. Despite bacterial factors, gastric environmental factors and host genetic constituents together play a co-operative role for gastric pathogenicity. The virulence factors include bacterial colonization factors BabA, SabA, OipA, and HopQ, and the virulence factors necessary for gastric pathogenicity include the effector proteins like CagA, VacA, HtrA, and the outer membrane vesicles. Bacterial factors are considered more important. Here, we summarize the recent information to better understand several bacterial virulence factors and their role in the pathogenic mechanism.

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Section: Virulence Factors Associated With Gastric Epithelial Cellmentioning

confidence: 99%

Helicobacter pylori Virulence Factors Exploiting Gastric Colonization and its Pathogenicity

Ansari

Yamaoka

2019

Toxins

174

141

View full text Add to dashboard Cite

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“…Since various cell types are able to activate the NF-κB pathway in response to TNF-α via TNFR1, the activation of NF-κB not only serves a crucial function in inhibiting apoptosis by inducing the upregulation of key antiapoptotic proteins, such as Bcl-2, Bcl-extra large and X-linked inhibitor of apoptosis protein (33,34), but may also perform a proapoptotic function (35,36). The results of the present study demonstrate that LRP1-knockdown chondrocytes exhibit increased susceptibility to cell death in response to TNF-α, as indicated by the TUNEL assay and the nucleic morphological alterations of apoptotic chondrocytes stained with 4' ,6-diamidino-2-phenylindole (Fig.…”

mentioning

confidence: 99%

Lentivirus-induced knockdown of LRP1 induces osteoarthritic-like effects and increases susceptibility to apoptosis in chondrocytes via the nuclear factor-κB pathway

Yang

Zheng

Peng

et al. 2015

Experimental and Therapeutic Medicine

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Low-density lipoprotein receptor-related protein 1 (LRP1) is known to regulate cell survival and inflammation. The present study investigated the involvement of LRP1 in the regulation of tumor necrosis factor (TNF)-α-induced expression of matrix metalloproteinase (MMP)-13. Furthermore, the study aimed to elucidate the mechanisms underlying the effects of LRP1 on TNF-α-induced inflammation and apoptosis of chondrocytes. Lentivirus-mediated RNA interference techniques were used to knockdown the LRP1 gene. Subsequently, the effects of LRP1 on TNF-α-induced MMP-13 expression were determined using quantitative polymerase chain reaction, western blot analysis and ELISA. Furthermore, the TNF-α-induced intracellular pathway was investigated using a nuclear factor (NF)-κB inhibitor (Bay 11-7082). In addition, the effect of LRP1 regulation on growth and apoptosis in chondrocytes was investigated using western blot analysis and a TUNEL assay. LRP1 knockdown was shown to increase TNF-α-induced MMP-13 expression via the activation of the NF-κB (p65) pathway, which reduced the expression of collagen type II and cell viability. In addition, LRP1 inhibited cell apoptosis by increasing the expression of phospho-Akt and B-cell lymphoma 2 (Bcl-2), while suppressing the expression of caspase-3 and Bcl-2-associated X protein. The results of the present study indicated that LRP1 was able to inhibit TNF-α-induced apoptosis and inflammation in chondrocytes. Therefore, LRP1 may be an effective osteoarthritis inhibitor, potentially providing a novel approach for antiarthritic therapeutics.

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“…As H. pylori can trigger STAT3, c-Jun, NF-jB and ERK activation in gastric carcinogenesis, [6][7][8][9]13,14 we next explored whether these proteins may regulate TMEFF2 expression. Gastric cells were treated with H. pylori after knockdown of STAT3, c-Jun, NF-jB and ERK, respectively.…”

Section: Tmeff2 Was Deregulated In H Pylori-related Gastric Carcinogmentioning

confidence: 99%

“…Helicobacter pylori ( H. pylori ) is considered as the strongest risk factor among the host genetic and environmental factors influencing the occurrence and progression of GCs . H. pylori triggers multiple pathways (JAK/STAT3, NF‐κB, PI3K/Akt, Wnt/β‐catenin and Ras/Erk) in gastric epithelial cells and induces complex alterations of these host signaling pathways . Dana et al demonstrated H. pylori induced STAT3 activation both in vitro and in vivo .…”

mentioning

confidence: 99%

“…cells and induces complex alterations of these host signaling pathways. [6][7][8][9][10][11][12][13][14] Dana et al demonstrated H. pylori induced STAT3 activation both in vitro and in vivo. Importantly, they found that the activation of STAT3 was dependent on translocation but not phosphorylation of cytotoxin-associated gene A (CagA), the most well-characterized H. pylori virulence determinant.…”

mentioning

confidence: 99%

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Bidirectional regulation between TMEFF2 and STAT3 may contribute to Helicobacter pylori‐associated gastric carcinogenesis

Sun

Tang

et al. 2014

Intl Journal of Cancer

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The transmembrane protein with epidermal growth factor and two follistatin motifs 2 (TMEFF2) is a single-pass transmembrane protein, and it is downregulated in human gastric cancer and levels correlate with tumor progression and time of survival. However, the mechanism of its dysregulation in gastric cancer is little known. Here we investigate its regulatory mechanism and the bidirectional regulation between TMEFF2 and STAT3 in gastric carcinogenesis. TMEFF2 expression was decreased after Helicobacter pylori (H. pylori) infection in vivo and in vitro. STAT3 directly binds to the promoter of TMEFF2 and regulates H. pylori-induced TMEFF2 downregulation in normal gastric GES-1 cells and gastric cancer AGS cells. Conversely, TMEFF2 may suppress the phosphorylation of STAT3 and TMEFF2-induced downregulation of STAT3 phosphorylation may depend on SHP-1. A highly inverse correlation between the expression of TMEFF2 and pSTAT3 was also revealed in gastric tissues. We now show the deregulation mechanism of TMEFF2 in gastric carcinogenesis and identify TMEFF2 as a new target gene of STAT3. The phosphorylation of STAT3 may be negatively regulated by TMEFF2, and the bidirectional regulation between TMEFF2 and STAT3 may contribute to H. pylori-associated gastric carcinogenesis.V C 2014 UICC Gastric cancer (GC) is the second leading cause of cancerrelated death worldwide.1 Most patients are diagnosed at an advantaged stage because of lack of early specific symptoms and eventually dead after operation because of recurrence and metastasis. 2,3Helicobacter pylori (H. pylori) is considered as the strongest risk factor among the host genetic and environmental factors influencing the occurrence and progression of GCs. 4,5 H. pylori triggers multiple pathways (JAK/STAT3, NF-jB, PI3K/Akt, Wnt/b-catenin and Ras/Erk) in gastric epithelial

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Overexpression ofHelicobacter pyloriVacA N-terminal fragment induces proinflammatory cytokine expression and apoptosis in human monocytic cell line through activation of NF-κB

Cited by 19 publications

References 50 publications

Helicobacter pylori Virulence Factors Exploiting Gastric Colonization and its Pathogenicity

Helicobacter pylori Virulence Factors Exploiting Gastric Colonization and its Pathogenicity

Lentivirus-induced knockdown of LRP1 induces osteoarthritic-like effects and increases susceptibility to apoptosis in chondrocytes via the nuclear factor-κB pathway

Bidirectional regulation between TMEFF2 and STAT3 may contribute to Helicobacter pylori‐associated gastric carcinogenesis

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