The Helicobacter pylori VacA cytotoxin activates RBL-2H3 cells by inducing cytosolic calcium oscillations.
Helicobacter pylori causes an acute inflammatory response followed by chronic infection of the human gastric mucosa. Identification of the bacterial molecules endowed with a pro-inflammatory activity is essential to a molecular understanding of the pathogenesis of H. pylori associated diseases. The vacuolating cytotoxin A (VacA) induces mast cells to release pro-inflammatory cytokines. Here, we show that VacA activates the mast cell line RBL-2H3 by rapidly inducing an oscillation of the level of cytosolic calcium with exocytosis of secretory granules. Cytosolic calcium derives mainly from intracellular stores. VacA also stimulates a calcium-dependent production of pro-inflammatory cytokines, including tumour necrosis factor alpha (TNF-alpha). These observations indicate that VacA may act as a pro-inflammatory factor of H. pylori at very early stages of the innate immune response.
de Bernard
Marina
M
Dipartimento di Biologia, Biomediche Sperimentali, Università di Padova, Via G Colombo 3, Padova, Italy. marina.debernard@unipd.it
Cappon
Andrea
A
Pancotto
Laura
L
Ruggiero
Paolo
P
Rivera
Juan
J
Del Giudice
Giuseppe
G
Montecucco
Cesare
C
D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D020013:Calcium Signaling; D015550:Cell Degranulation; D002460:Cell Line; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005089:Exocytosis; D016481:Helicobacter Infections / Q000276:immunology* / Q000382:microbiology; D016480:Helicobacter pylori / Q000502:physiology*; D008407:Mast Cells / Q000276:immunology*; D012333:RNA, Messenger; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C074689:VacA protein, Helicobacter pylori; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid