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Lactobacillus rhamnosus GR-1 enhances NF-kappaB activation in Escherichia coli-stimulated urinary bladder cells through TLR4
Örebro University, School of Science and Technology.
Örebro University, School of Science and Technology.ORCID iD: 0000-0001-9713-2365
Department of Microbiology and Immunology, University of Western Ontario, London ON, Canada.
Örebro University, School of Science and Technology.ORCID iD: 0000-0001-7957-0310
2012 (English)In: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 12, p. 15-Article in journal (Refereed) Published
Abstract [en]

Background: Epithelial cells of the urinary tract recognize pathogenic bacteria through pattern recognition receptors on their surface, such as toll-like receptors (TLRs), and mount an immune response through the activation of the NF-kappaB pathway. Some uropathogenic bacteria can subvert these cellular responses, creating problems with how the host eliminates pathogens. Lactobacillus is a genus of lactic acid bacteria that are part of the microbiota and consist of many probiotic strains, some specifically for urogenital infections. Immunomodulation has emerged as an important mode of action of probiotic and commensal lactobacilli and given the importance of epithelial cells, we evaluated the effect of the urogenital probiotic Lactobacillus rhamnosus GR-1 on epithelial immune activation.

Results: Immune activation through the NF-kappaB pathway was initiated by stimulation of T24 urothelial cells with heat-killed Escherichia coli and this was further potentiated when cells were co-cultured with live L. rhamnosus GR-1. Heat-killed lactobacilli were poor activators of NF-kappaB. Concomitant stimulation of bladder cells with E. coli and L. rhamnosus GR 1 increased the levels of the pro-inflammatory cytokine TNF, whereas IL-6 and CXCL8 levels were reduced. Another probiotic, L. rhamnosus GG, was also able to potentiate NF-kappaB in these cells although at a significantly reduced level compared to the GR 1 strain. The transcript numbers and protein levels of the lipopolysaccharide receptor TLR4 were significantly increased after co-stimulation with E. coli and lactobacilli compared to controls. Furthermore, inhibition of TLR4 activation by polymixin B completely blocked the lactobacilli potentiation of NF-kappaB.

Conclusions: The immunological outcome of E. coli challenge of bladder cells was influenced by probiotic L. rhamnosus GR 1, by enhancing the activation of NF-kappaB and TNF release. Thus the urogenital probiotic L. rhamnosus GR-1 modulated the activation of the NF-kappaB through increased levels of TLR4 on the bladder cells and altered subsequent release of cytokines from urothelial cells. By influencing immunological factors such as TLR4, important in the process of fighting pathogens, lactobacilli could facilitate pathogen recognition and infection clearance.

Place, publisher, year, edition, pages
BioMed Central, 2012. Vol. 12, p. 15-
National Category
Microbiology
Research subject
Microbiology; Immunology
Identifiers
URN: urn:nbn:se:oru:diva-21288DOI: 10.1186/1471-2180-12-15ISI: 000301484000001PubMedID: 22264349Scopus ID: 2-s2.0-84856001528OAI: oai:DiVA.org:oru-21288DiVA, id: diva2:504084
Available from: 2012-02-17 Created: 2012-01-24 Last updated: 2018-05-08Bibliographically approved
In thesis
1. Modulation of cellular innate immune responses by lactobacilli
Open this publication in new window or tab >>Modulation of cellular innate immune responses by lactobacilli
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Lactobacillus is a genus of lactic acid bacteria frequently used as healthpromoting probiotics. Using probiotics to treat or prevent infections is a novel experimental approach with vast impact on future therapy. Lactobacillus rhamnosus GR-1 is a probiotic investigated for its ability to reduce urogenital disease including urinary tract infections caused by pathogenic Escherichia coli. L. rhamnosus GR-1 has been shown to modulate immunity, thought to influence its probiotic effect. In this thesis, the aim was to study immunomodulation by L. rhamnosus GR-1 and other lactobacilli, with emphasis on elicited immune responses such as nuclear factor-kappaB (NF-κB) activation and cytokine release from human urothelial cells.

Viable, heat-killed, and isolated released products from L. rhamnosus GR-1 augmented NF-κB activation in E. coli-challenged urothelial cells. Blocking of lipopolysaccharide binding to toll-like receptor 4 completely quelled this augmentation. Size-fractionation, urothelial cell challenge, and two-dimensional gel electrophoresis of L. rhamnosus GR-1 released products presented several candidate proteins with NF-κB modulatory actions including chaperonin GroEL, elongation factur Tu, and a protein from the NLP/P60 protein family. While tumor necrosis factor was correspondingly augmented by L. rhamnosus GR-1, the release of two other cytokines, interleukin (IL)-6 and CXCL8, was reduced. Similar effects were observed in macrophage-like cells stimulated with L. rhamnosus GR-1.

Many immunomodulatory effects of lactobacilli are believed to be species and strain dependent. Therefore, twelve Lactobacillus strains were used to screen for their effects on CXCL8 release from urothelial cells. A majority of these strains were able to influence CXCL8 release from the cells. Phylogenetic analysis revealed close evolutionary linkage between lactobacilli with similar actions on CXCL8. Increased knowledge on probiotic bacterial products and the mechanism(s) of action could lead to improved future treatments for infections.

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2012. p. 84
Series
Örebro Studies in Life Science ; 10
Keywords
cytokines, immunomodulation, lactobacilli, probiotics, urinary tract infections, urothelium
National Category
Biological Sciences
Research subject
Biology
Identifiers
urn:nbn:se:oru:diva-22138 (URN)978-91-7668-872-4 (ISBN)
Public defence
2012-06-01, Hörsal BIO, Forumhuset, Örebro universitet, Fakultetsgatan 1, Örebro, 13:00 (English)
Opponent
Supervisors
Available from: 2012-03-16 Created: 2012-03-16 Last updated: 2017-10-17Bibliographically approved

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Karlsson, MattiasScherbak, NikolaiJass, Jana

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