Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/43606
Title: Probiotic Sonicates Selectively Induce Mucosal Immune Cells Apoptosis Through Ceramide Generation Via Neutral Sphingolyelinase.
Author: Angulo, Sandra
Morales, Albert
Danese, Silvio
Llacuna, Laura
Masamunt, Maris Carme
Pultz, Nicole
Cifone, Maria Grazia
De Simone, Claudio
Delgado Rivilla, Salvadora
Vila Estapé, Jordi
Panés Díaz, Julià
Donskey, Curtis
Fernández-Checa, Jose C.
Fiocchi, Claudio
Sans, 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
Related resource: http://dx.doi.org/10.1371/journal.pone.0016953
URI: http://hdl.handle.net/2445/43606
ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Fonaments Clínics)

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