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Lactobacilli differently regulate expression and secretion of CXCL8 in urothelial cells
Örebro University, School of Science and Technology.
Örebro University, School of Science and Technology.ORCID iD: 0000-0001-7957-0310
2012 (English)In: Beneficial Microbes, ISSN 1876-2883, E-ISSN 1876-2891, Vol. 3, no 3, p. 195-203Article in journal (Refereed) Published
Abstract [en]

Modulation of the immune response is an established feature of certain lactobacilli. CXCL8 is an inflammatory chemokine released by the urinary tract mucosa after contact with uropathogenic Escherichia coli during urinary tract infection and is crucial for proper infiltration of immune cells. Nevertheless, persistently high levels of CXCL8 are associated with pathogenicity and malignancy. In this study, we tested twelve Lactobacillus strains for their ability to influence CXCL8 release from urothelial cells. We evaluated how strains from different Lactobacillus species could regulate CXCL8 in human 5637 urothelial cells, either resting cells or cells concomitantly challenged with heat-killed E. coli. A majority of the tested species altered CXCL8 release from the urothelial cells after 24 hours of stimulation. Most species increased CXCL8 release, whereas a few lactobacilli efficiently suppressed CXCL8 secretion from E. coli-challenged cells. While strong CXCL8 modulators such as Lactobacillus reuteri and Lactobacillus delbrueckii were unable to degrade CXCL8 in the extracellular environment, effects on IL8 transcription were evident for selected lactobacilli. Although IL8 transcription was affected by lactobacilli, the influence on mRNA transcript did not correlate to the impact on CXCL8 release. Phylogenetic analysis based on a 16S rRNA dendrogram of the tested lactobacilli and their effect on CXCL8 revealed some linkage to specific Lactobacillus groups. Testing the immunomodulatory nature of lactobacilli can prove important when selecting new probiotic microbes. Moreover, we believe that phylogenetic and phenotypic similarities could be used to analyse the traits governing such modulation.

Place, publisher, year, edition, pages
Wageningen Academic Publishers, 2012. Vol. 3, no 3, p. 195-203
Keywords [en]
Lactobacillus; immunomodulation; probiotics; chemokines; cytokines
National Category
Microbiology Nutrition and Dietetics
Research subject
Immunology; Microbiology; Nutrition
Identifiers
URN: urn:nbn:se:oru:diva-21701DOI: 10.3920/BM2012.0011ISI: 000308740900004PubMedID: 22835703Scopus ID: 2-s2.0-84869221939OAI: oai:DiVA.org:oru-21701DiVA, id: diva2:516811
Funder
Knowledge Foundation
Note

Funding Agencies:

Magnus Bergvalls Foundation

Helge Ax:son Johnsons Foundation 

Available from: 2012-04-19 Created: 2012-02-17 Last updated: 2017-12-07Bibliographically 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, MattiasJass, Jana

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