The Helicobacter pylori VacA cytotoxin activates RBL-2H3 cells by inducing cytosolic calcium oscillations |
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| Authors: | de Bernard Marina Cappon Andrea Pancotto Laura Ruggiero Paolo Rivera Juan Del Giudice Giuseppe Montecucco Cesare |
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| Institution: | Dipartimento di Biologia;and Dipartimento di Scienze Biomediche Sperimentali, Universitàdi Padova, Via G. Colombo 3, Padova, Italy.; Istituto Veneto di Medicina Molecolare, Via Orus 2, Padova, Italy.; IRIS CHIRON SpA, Via Fiorentina 1, Siena, Italy.; National Institute of Arthritis and Musculoskeletal and Skin Diseases/National Institutes of Health, Bethesda, MD 20892, USA. |
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| Abstract: | 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. |
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