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Title: | Probiotic Sonicates Selectively Induce Mucosal Immune Cells Apoptosis Through Ceramide Generation Via Neutral Sphingolyelinase |
Author: | Angulo, Sandra Morales Muñoz, Albert Danese, Silvio Llacuna Durán, Laura Masamunt, Maria Carme Pultz, Nicole Cifone, Maria Grazia De Simone, Claudio Delgado Rivilla, Salvadora Vila Estapé, Jordi Panés Díaz, Julià Donskey, Curtis Fernández-Checa Torres, José Carlos Fiocchi, Claudio Sans i Cuffí, Miquel |
Keywords: | Malalties inflamatòries intestinals Probiòtics Inflammatory bowel diseases Probiotics |
Issue Date: | 9-Mar-2011 |
Publisher: | Public Library of Science (PLoS) |
Abstract: | Background: Probiotics appear to be beneficial in inflammatory bowel disease, but their mechanism of action is incompletely understood. We investigated whether probiotic-derived sphingomyelinase mediates this beneficial effect. Methodology/Principal Findings: Neutral sphingomyelinase (NSMase) activity was measured in sonicates of the probiotic L.brevis (LB)and S. thermophilus (ST) and the non-probiotic E. coli EC) and E. faecalis (EF). Lamina propria mononuclear cells (LPMC) were obtained from patients with Crohn"s disease (CD) and Ulcerative Colitis (UC), and peripheral blood mononuclear cells (PBMC) from healthy volunteers, analysing LPMC and PBMC apoptosis susceptibility, reactive oxygen species (ROS) generation and JNK activation. In some experiments, sonicates were preincubated with GSH or GW4869, a specific NSMase inhibitor. NSMase activity of LB and ST was 10-fold that of EC and EF sonicates. LB and ST sonicates induced significantly more apoptosis of CD and UC than control LPMC, whereas EC and EF sonicates failed to induce apoptosis. Pre-stimulation with anti-CD3/CD28 induced a significant and time-dependent increase in LB-induced apoptosis of LPMC and PBMC. Exposure to LB sonicates resulted in JNK activation and ROS production by LPMC. NSMase activity of LB sonicates was completely abrogated by GW4869, causing a dose-dependent reduction of LB -induced poptosis. LB and ST selectively induced immune cell apoptosis, an effect dependent on the degree of cell activation and mediated by bacterial NSMase. Conclusions: These results suggest that induction of immune cell apoptosis is a mechanism of action of some probiotics and that NSMase-mediated ceramide generation contributes to the therapeutic effects of probiotics. |
Note: | Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0016953 |
It is part of: | PLoS One, 2011, vol. 6, num. 3, p. e16953 |
URI: | http://hdl.handle.net/2445/43606 |
Related resource: | http://dx.doi.org/10.1371/journal.pone.0016953 |
ISSN: | 1932-6203 |
Appears in Collections: | Articles publicats en revistes (Fonaments Clínics) |
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