Bacteria-free solution derived from lactobacillus plantarum inhibits multiple NF-kappaB pathways and inhibits proteasome function
Open Access
- 1 October 2009
- journal article
- research article
- Published by Oxford University Press (OUP) in Inflammatory Bowel Diseases
- Vol. 15 (10), 1537-1547
- https://doi.org/10.1002/ibd.20930
Abstract
Bacteria play a role in inflammatory bowel disease and other forms of intestinal inflammation. Although much attention has focused on the search for a pathogen or inciting inflammatory bacteria, another possibility is a lack of beneficial bacteria that normally confer anti-inflammatory properties in the gut. The purpose of this study was to determine whether normal commensal bacteria could inhibit inflammatory pathways important in intestinal inflammation. Conditioned media from Lactobacillus plantarum (Lp-CM) and other gut bacteria was used to treat intestinal epithelial cell (YAMC) and macrophage (RAW 264.7) or primary culture murine dendritic cells. NF-κB was activated through TNF-Receptor, MyD88-dependent and -independent pathways and effects of Lp-CM on the NF-κB pathway were assessed. NF-κB binding activity was measured using ELISA and EMSA. 1κB expression was assessed by Western blot analysis, and proteasome activity determined using fluorescence-based proteasome assays. MCP-1 release was determined by ELISA. Lp-CM inhibited NF-κB binding activity, degradation of IκBα and the chymotrypsin-like activity of the proteasome. Moreover, Lp-CM directly inhibited the activity of purified mouse proteasomes. This effect was specific, since conditioned media from other bacteria had no inhibitory effect. Unlike other proteasome inhibitors, Lp-CM was not toxic in cell death assays. Lp-CM inhibited MCP-1 release in all cell types tested. These studies confirm, and provide a mechanism for, the anti-inflammatory effects of the probiotic and commensal bacterium Lactobacillus plantarum. The use of bacteria-free Lp-CM provides a novel strategy for treatment of intestinal inflammation which would eliminate the risk of bacteremia reported with conventional probiotics.Keywords
This publication has 54 references indexed in Scilit:
- Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patientsProceedings of the National Academy of Sciences of the United States of America, 2008
- Bacteria in the Intestine, Helpful Residents or Enemies from Within?Infection and Immunity, 2008
- Interplay of commensal and pathogenic bacteria, genetic mutations, and immunoregulatory defects in the pathogenesis of inflammatory bowel diseasesJournal of Internal Medicine, 2008
- The therapeutic potential of the proteasome in leukaemiaHematological Oncology, 2008
- Human gut microbes associated with obesityNature, 2006
- Proteasome-mediated degradation of IκBα and processing of p105 in Crohn disease and ulcerative colitisJCI Insight, 2006
- An obesity-associated gut microbiome with increased capacity for energy harvestNature, 2006
- Maintenance of colonic homeostasis by distinctive apical TLR9 signalling in intestinal epithelial cellsNature, 2006
- Host-Bacterial Mutualism in the Human IntestineScience, 2005
- Safety ofLactobacillusStrains Used as Probiotic AgentsClinical Infectious Diseases, 2002