PloS one, 2011-03, Vol.6 (3), p.e16953-e16953
2011
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- Autor(en) / Beteiligte
- Titel
- Probiotic sonicates selectively induce mucosal immune cells apoptosis through ceramide generation via neutral sphingomyelinase
- Ist Teil von
- PloS one, 2011-03, Vol.6 (3), p.e16953-e16953
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2011
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. 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 apoptosis. LB and ST selectively induced immune cell apoptosis, an effect dependent on the degree of cell activation and mediated by bacterial NSMase. 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0016953Titel-ID: cdi_plos_journals_1295943694
- Format
- –
- Schlagworte
- Aniline Compounds - pharmacology, Apoptosis, Apoptosis - drug effects, Bacteria, Benzylidene Compounds - pharmacology, Biology, Breakdowns, c-Jun amino-terminal kinase, CD28 antigen, CD3 antigen, Cell activation, Cell cycle, Ceramide, Ceramides - biosynthesis, Ceramides - pharmacology, Crohn's disease, Crohns disease, E coli, Enterobacteriaceae - drug effects, Enterobacteriaceae - enzymology, Enterococcus faecalis, Enzyme Activation - drug effects, Enzyme Inhibitors - pharmacology, Enzymes, Escherichia coli, Extracellular matrix, Gastroenterology, Glutathione - pharmacology, Hospitals, Humans, Immune system, Immunity, Mucosal - drug effects, Infectious diseases, Inflammatory bowel disease, Inflammatory bowel diseases, Intestine, JNK Mitogen-Activated Protein Kinases - metabolism, JNK protein, Lactobacillus brevis, Lamina propria, Leukocytes (mononuclear), Leukocytes, Mononuclear - cytology, Leukocytes, Mononuclear - drug effects, Leukocytes, Mononuclear - enzymology, Lipids, Lymphocytes, Medicine, Mucosal immunity, Mucous Membrane - cytology, Mucous Membrane - enzymology, Oxidative stress, Oxygen, Peripheral blood mononuclear cells, Phosphorylation - drug effects, Probiotics, Probiotics - pharmacology, Reactive oxygen species, Reactive Oxygen Species - metabolism, Sonication, Sphingomyelin phosphodiesterase, Sphingomyelin Phosphodiesterase - antagonists & inhibitors, Sphingomyelin Phosphodiesterase - metabolism, Sphingomyelin Phosphodiesterase - pharmacology, Streptococcus thermophilus, Transcription factors, Ulcerative colitis