Induction of TNF, CXCL8 and IL-1β in macrophages by Helicobacter pylori secreted protein HP1173 occurs via MAP-kinases, NF-κB and AP-1 signaling pathways

2018 ◽  
Vol 125 ◽  
pp. 295-305 ◽  
Author(s):  
Raquel Tavares ◽  
Sushil Kumar Pathak
Keyword(s):  
Helicobacter Pylori ◽  
Signaling Pathways ◽  
Map Kinases ◽  
Secreted Protein

scholarly journals Serological Assays for Identification of Human Gastric Colonization by Helicobacter pylori Strains Expressing VacA m1 or m2

2007 ◽  
Vol 14 (4) ◽  
pp. 442-450 ◽  
Author(s):  
Chandrabali Ghose ◽  
Guillermo I. Perez-Perez ◽  
Victor J. Torres ◽  
Marialuisa Crosatti ◽  
Abraham Nomura ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Asian American ◽  
Specific Antigen ◽  
Secreted Protein ◽  
Gastric Epithelial Cells ◽  
Allele Specific ◽  
Risk Of Disease ◽  
Specific Antigens ◽  
H Pylori ◽  
Development Of Gastric Cancer

ABSTRACT The Helicobacter pylori vacA gene encodes a secreted protein (VacA) that alters the function of gastric epithelial cells and T lymphocytes. H. pylori strains containing particular vacA alleles are associated with differential risk of disease. Because the VacA midregion may exist as one of two major types, m1 or m2, serologic responses may potentially be used to differentiate between patients colonized with vacA m1- or vacA m2-positive H. pylori strains. In this study, we examined the utility of specific antigens from the m regions of VacA as allele-specific diagnostic antigens. We report that serological responses to P44M1, an H. pylori m1-specific antigen, are observed predominantly in patients colonized with m1-positive strains, whereas responses to VacA m2 antigens, P48M2 and P55M2, are observed in patients colonized with either m1- or m2-positive strains. In an Asian-American population, serologic responses to VacA m region-specific antigens were not able to predict the risk of development of gastric cancer.

scholarly journals Helicobacter Pylori Targets the EPHA2 Receptor Tyrosine Kinase in Gastric Cells Modulating Key Cellular Functions

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 513 ◽  
Author(s):  
Marina Leite ◽  
Miguel S. Marques ◽  
Joana Melo ◽  
Marta T. Pinto ◽  
Bruno Cavadas ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Tyrosine Kinase ◽  
Signaling Pathways ◽  
Receptor Tyrosine Kinase ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Receptor Activation ◽  
Degradation Pathway ◽  
Mrna Levels ◽  
H Pylori

Helicobacter pylori, a stomach-colonizing Gram-negative bacterium, is the main etiological factor of various gastroduodenal diseases, including gastric adenocarcinoma. By establishing a life-long infection of the gastric mucosa, H. pylori continuously activates host-signaling pathways, in particular those associated with receptor tyrosine kinases. Using two different gastric epithelial cell lines, we show that H. pylori targets the receptor tyrosine kinase EPHA2. For long periods of time post-infection, H. pylori induces EPHA2 protein downregulation without affecting its mRNA levels, an effect preceded by receptor activation via phosphorylation. EPHA2 receptor downregulation occurs via the lysosomal degradation pathway and is independent of the H. pylori virulence factors CagA, VacA, and T4SS. Using small interfering RNA, we show that EPHA2 knockdown affects cell–cell and cell–matrix adhesion, invasion, and angiogenesis, which are critical cellular processes in early gastric lesions and carcinogenesis mediated by the bacteria. This work contributes to the unraveling of the underlying mechanisms of H. pylori–host interactions and associated diseases. Additionally, it raises awareness for potential interference between H. pylori infection and the efficacy of gastric cancer therapies targeting receptors tyrosine kinases, given that infection affects the steady-state levels and dynamics of some receptor tyrosine kinases (RTKs) and their signaling pathways.

scholarly journals Inflammatory signaling pathways induced by Helicobacter pylori in primary human gastric epithelial cells

2016 ◽  
Vol 23 (2) ◽  
pp. 165-174 ◽  
Author(s):  
Cong Tri Tran ◽  
Magali Garcia ◽  
Martine Garnier ◽  
Christophe Burucoa ◽  
Charles Bodet
Keyword(s):  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Mrna Expression ◽  
Signaling Pathways ◽  
Post Infection ◽  
Gastric Epithelial Cells ◽  
Inflammatory Signaling ◽  
Independent Manner ◽  
Chemokine Production ◽  
H Pylori

Inflammatory signaling pathways induced by Helicobacter pylori remain unclear, having been studied mostly on cell-line models derived from gastric adenocarcinoma with potentially altered signaling pathways and nonfunctional receptors. Here, H. pylori-induced signaling pathways were investigated in primary human gastric epithelial cells. Inflammatory response was analyzed on chemokine mRNA expression and production after infection of gastric epithelial cells by H. pylori strains, B128 and B128Δ cagM, a cag type IV secretion system defective strain. Signaling pathway involvement was investigated using inhibitors of epidermal growth factor receptor (EGFR), MAPK, JAK and blocking Abs against TLR2 and TLR4. Inhibitors of EGFR, MAPK and JAK significantly reduced the chemokine mRNA expression and production induced by both H. pylori strains at 3 h and 24 h post-infection. JNK inhibitor reduced chemokine production at 24 h post-infection. Blocking Abs against TLR2 but not TLR4 showed significant reduction of chemokine secretion. Using primary culture of human gastric epithelial cells, our data suggest that H. pylori can be recognized by TLR2, leading to chemokine induction, and that EGFR, MAPK and the JAK/STAT signaling pathways play a key role in the H. pylori-induced CXCL1, CXCL5 and CXCL8 response in a cag pathogenicity island-independent manner.

The Effect of Adenosine on TLR Signaling Pathways in Human Monocytic THP-1 Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3828-3828
Author(s):  
Chin-Fu Chen ◽  
Chun-Huai Cheng ◽  
Seychelle Vos
Keyword(s):  
Immune Responses ◽  
Signaling Pathways ◽  
Immune Cells ◽  
Adenosine Receptors ◽  
Protein Modification ◽  
Map Kinases ◽  
Critical Role ◽  
Innate Immune ◽  
Fcγ Receptors ◽  
Tlr Signaling

Abstract Adenosine is an important metabolite that serves as a potent regulator of inflammation and mediates various biological functions in different cell types. Adenosine inhibits the proinflammatory actions of inflammatory and immune cells via interaction with its receptors, particularly A2A receptors. Adenosine receptors belong to the seven-transmembrane G-protein coupled receptors and via the different G proteins transfer signals through different effectors including adenyl cyclase, PKA, PKC, PI3K, and MAP kinases. The mechanisms by which the adenosine regulates immune responses and how adenosine receptor pathways interact with other signaling pathways are currently unknown. Toll-like receptors (TLRs) of the innate immune cells recognize conserved microbial structures, such as bacterial lipopolysaccharide and viral double-stranded RNA, and activate signaling pathways that result in innate immune responses against microbial infections. Fcγ receptors of the innate cells play a critical role in the clearance of pathogens, regulation of inflammation and co-ordination of the immune response. We seek to understand the interaction between adenosine (via adenosine receptors) and TLR- and Fcγ R- mediated signaling pathways. We have initiated study on the effect of adenosine and lipopolysaccharide (LPS) on expression of TLR2, TLR4, FcγRI and Fcγ RII receptors in the human monocytic cell line THP-1. We incubated cells with 100μM adenosine for three hours at 37°C and assayed the expression of receptors using flow cytometry. Our results suggest that adenosine increases the expression of TLR2 and TLR4 in both undifferentiated cells and the cells induced to become macrophages by phorbol ester. Incubation with adenosine for 24 hours further increases the expression of TLR2 and TLR4 in both undifferentiated and differentiated THP-1 cells. Similarly, incubation with LPS for three hours increases the expression TLR2 and TLR4 in both undifferentiated and differentiated THP-1 cells. In contrast, the expression level of FcγRI and FcγRII receptors do not change in the presence of either adenosine or LPS. These observations suggest that adenosine specifically enhances expression of TLRs but not Fcγ receptors. To further understand the interaction between adenosine and TLR pathways, we are continuously investigating the effect of adenosine on expression and the protein modification (e.g. phosphorylation) of TLR2, TLR4, and the molecules in the TLR signaling cascades including MyD88, IRAK and MAP kinases using real-time RT-PCR and western blotting.

MAP kinases‐Regulated Proteins in Downstream Signaling Pathways of Vasopressin V2 Receptor in Kidney Collecting Duct

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Hyo-Ju Jang ◽  
Hyun jun Jung ◽  
Hyo-Jung Choi ◽  
Eui-Jung Park ◽  
Hye-Jeong Park ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Map Kinases ◽  
Collecting Duct ◽  
Downstream Signaling ◽  
Kidney Collecting Duct ◽  
Vasopressin V2 Receptor ◽  
V2 Receptor

MAP kinases and the adaptive response to hypertonicity: functional preservation from yeast to mammals

2004 ◽  
Vol 287 (6) ◽  
pp. F1102-F1110 ◽  
Author(s):  
David Sheikh-Hamad ◽  
Michael C. Gustin
Keyword(s):  
Transcription Factors ◽  
Signaling Pathways ◽  
Adaptive Response ◽  
Mammalian Cells ◽  
Map Kinases ◽  
Current Knowledge ◽  
Cis Elements ◽  
P38 Kinase ◽  
Functional Preservation ◽  
Multiple Signaling

The adaptation to hypertonicity in mammalian cells is driven by multiple signaling pathways that include p38 kinase, Fyn, the catalytic subunit of PKA, ATM, and JNK2. In addition to the well-characterized tonicity enhancer (TonE)-TonE binding protein interaction, other transcription factors (and their respective cis elements) can potentially respond to hypertonicity. This review summarizes the current knowledge about the signaling pathways that regulate the adaptive response to osmotic stress and discusses new insights from yeast that could be relevant to the osmostress response in mammals.

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