oru.sePublikationer
Ändra sökning
Länk till posten
Permanent länk

Direktlänk
BETA
Publikationer (10 of 23) Visa alla publikationer
Geng, D., Musse, A. A., Wigh, V., Carlsson, C., Engwall, M., Oresic, M., . . . Hyötyläinen, T. (2019). Effect of perfluorooctanesulfonic acid (PFOS) on the liver lipid metabolism of the developing chicken embryo. Ecotoxicology and Environmental Safety, 170, 691-698
Öppna denna publikation i ny flik eller fönster >>Effect of perfluorooctanesulfonic acid (PFOS) on the liver lipid metabolism of the developing chicken embryo
Visa övriga...
2019 (Engelska)Ingår i: Ecotoxicology and Environmental Safety, ISSN 0147-6513, E-ISSN 1090-2414, Vol. 170, s. 691-698Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Perfluorooctanesulfonate (PFOS) is a well-known contaminant in the environment and it has shown to disrupt multiple biological pathways, particularly those related with lipid metabolism. In this study, we have studied the impact of in ovo exposure to PFOS on lipid metabolism in livers in developing chicken embryos using lipidomics for detailed characterization of the liver lipidome. We used an avian model (Gallus gallus domesticus) for in ovo treatment at two levels of PFOS. The lipid profile of the liver of the embryo was investigated by ultra-high performance liquid chromatography combined with quadrupole-time-of-flight mass spectrometry and by gas chromatography mass spectrometry. Over 170 lipids were identified, covering phospholipids, ceramides, di- and triacylglycerols, cholesterol esters and fatty acid composition of the lipids. The PFOS exposure caused dose dependent changes in the lipid levels, which included upregulation of specific phospholipids associated with the phosphatidylethanolamine N-methyltransferase (PEMT) pathway, triacylglycerols with low carbon number and double bond count as well as of lipotoxic ceramides and diacylglycerols. Our data suggest that at lower levels of exposure, mitochondrial fatty acid β-oxidation is suppressed while the peroxisomal fatty acid β -oxidation is increased. At higher doses, however, both β -oxidation pathways are upregulated.

Ort, förlag, år, upplaga, sidor
Elsevier, 2019
Nyckelord
Avian model, Lipidomics, Liver metabolism, Mass spectrometry, Perfluorooctanesulfonate
Nationell ämneskategori
Farmaceutiska vetenskaper
Identifikatorer
urn:nbn:se:oru:diva-71192 (URN)10.1016/j.ecoenv.2018.12.040 (DOI)000456890700083 ()30580163 (PubMedID)2-s2.0-85058940877 (Scopus ID)
Forskningsfinansiär
Vetenskapsrådet, 2016-05176Forskningsrådet FormasKK-stiftelsen
Tillgänglig från: 2019-01-08 Skapad: 2019-01-08 Senast uppdaterad: 2019-03-04Bibliografiskt granskad
Blanc, M., Rüegg, J., Scherbak, N. & Keiter, S. (2019). Environmental chemicals differentially affect epigenetic-related mechanisms in the zebrafish liver (ZF-L) cell line and in zebrafish embryos. Aquatic Toxicology, 215, Article ID 105272.
Öppna denna publikation i ny flik eller fönster >>Environmental chemicals differentially affect epigenetic-related mechanisms in the zebrafish liver (ZF-L) cell line and in zebrafish embryos
2019 (Engelska)Ingår i: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 215, artikel-id 105272Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

A number of chemicals have been shown to affect epigenetic patterning and functions. Since epigenetic mechanisms regulate transcriptional networks, epigenetic changes induced by chemical exposure can represent early molecular events for long-term adverse physiological effects. Epigenetics has thus appeared as a research field of major interest within (eco)toxicological sciences. The present study aimed at measuring effects on epigenetic-related mechanisms of selected environmental chemicals (bisphenols, perfluorinated chemicals, methoxychlor, permethrin, vinclozolin and coumarin 47) in zebrafish embryos and liver cells (ZFL). Transcription of genes related to DNA methylation and histone modifications was measured and global DNA methylation was assessed in ZFL cells using the LUMA assay. The differences in results gathered from both models suggest that chemicals affect different mechanisms related to epigenetics in embryos and cells. In zebrafish embryos, exposure to bisphenol A, coumarin 47, methoxychlor and permethrin lead to significant transcriptional changes in epigenetic factors suggesting that they can impact early epigenome reprogramming related to embryonic development. In ZFL cells, significant transcriptional changes were observed upon exposure to all chemicals but coumarin 47; however, only perfluorooctane sulfonate induced significant effects on global DNA methylation. Notably, in contrast to the other tested chemicals, perfluorooctane sulfonate affected only the expression of the histone demethylase kdm5ba. In addition, kdm5ba appeared as a sensitive gene in zebrafish embryos as well. Taken together, the present results suggest a role for kdm5ba in regulating epigenetic patterns in response to chemical exposure, even though mechanisms remain unclear. To confirm these findings, further evidence is required regarding changes in site-specific histone marks and DNA methylation together with their long-term effects on physiological outcomes.

Ort, förlag, år, upplaga, sidor
Elsevier, 2019
Nyckelord
Chemical pollutant, DNA methylation, Danio rerio, Histone modification, LUMA, qPCR
Nationell ämneskategori
Utvecklingsbiologi
Identifikatorer
urn:nbn:se:oru:diva-77033 (URN)10.1016/j.aquatox.2019.105272 (DOI)000489354800005 ()31442592 (PubMedID)2-s2.0-85070872497 (Scopus ID)
Forskningsfinansiär
Forskningsrådet Formas
Anmärkning

Funding Agency:

EnForce platform - KK Foundation  201660019

Tillgänglig från: 2019-10-07 Skapad: 2019-10-07 Senast uppdaterad: 2019-10-25Bibliografiskt granskad
Jacobsen, A. V., Nordén, M., Engwall, M. & Scherbak, N. (2018). Effects of perfluorooctane sulfonate on genes controlling hepatic fatty acid metabolism in livers of chicken embryos. Environmental science and pollution research international, 25(23), 23074-23081
Öppna denna publikation i ny flik eller fönster >>Effects of perfluorooctane sulfonate on genes controlling hepatic fatty acid metabolism in livers of chicken embryos
2018 (Engelska)Ingår i: Environmental science and pollution research international, ISSN 0944-1344, E-ISSN 1614-7499, Vol. 25, nr 23, s. 23074-23081Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Per- and polyfluoroalkyl substances (PFAS) are synthetic surfactants with a wide variety of applications; however, due to their stability, they are particularly resistant to degradation and, as such, are classed as persistent organic pollutants. Perfluorooctane sulfonate (PFOS) is one such PFAS that is still detectable in a range of different environmental settings, despite its use now being regulated in numerous countries. Elevated levels of PFOS have been detected in various avian species, and the impact of this on avian health is of interest when determining acceptable levels of PFOS in the environment. Due to its similarities to naturally occurring fatty acids, PFOS has potential to disrupt a range of biological pathways, particularly those associated with lipid metabolism, and this has been shown in various species. In this study, we have investigated how in ovo exposure to environmentally relevant levels of PFOS affects expression of genes involved in lipid metabolism of developing chicken embryos. We have found a broad suppression of transcription of genes involved in fatty acid oxidation and PPAR-mediated transcription with more significant effects apparent at lower doses of PFOS. These results highlight the need for more research investigating the biological impacts of low levels of PFAS to properly inform environmental policy governing their regulation.

Ort, förlag, år, upplaga, sidor
Springer Berlin/Heidelberg, 2018
Nyckelord
Perfluorooctane sulfonate, PFOS, In ovo, Chicken, Beta oxidation, qPCR array
Nationell ämneskategori
Miljövetenskap
Identifikatorer
urn:nbn:se:oru:diva-68542 (URN)10.1007/s11356-018-2358-7 (DOI)000441007000065 ()29860686 (PubMedID)2-s2.0-85047951738 (Scopus ID)
Forskningsfinansiär
Magnus Bergvalls Stiftelse
Anmärkning

Funding Agencies:

Örebro University

EnForce project - Knowledge Foundation 

Tillgänglig från: 2018-08-22 Skapad: 2018-08-22 Senast uppdaterad: 2018-08-22Bibliografiskt granskad
Delbro, D., Hallsberg, L., Peeker, R., Scherbak, N., Fall, M. & Godtman, R. A. (2018). The extracellular matrix-degrading protein ADAMTS5 is expressed in the nuclei of urothelial cells in healthy rats. Scandinavian journal of urology, 52(2), 139-142
Öppna denna publikation i ny flik eller fönster >>The extracellular matrix-degrading protein ADAMTS5 is expressed in the nuclei of urothelial cells in healthy rats
Visa övriga...
2018 (Engelska)Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 52, nr 2, s. 139-142Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

OBJECTIVE: The aim of this study was to investigate whether protein expression of the extracellular matrix-degrading protease ADAMTS5 can be demonstrated in the urinary bladder of healthy rats, and, if so, to determine the localization of this enzyme.

MATERIALS AND METHODS: The experiments were conducted with eight inbred male Sprague-Dawley rats. Immunohistochemistry was used to investigate the expression of ADAMTS5 in the urinary bladder. Negative controls were established by either excluding the primary antibody or applying the antibody after it had been preabsorbed with its immunogenic peptide. Confocal microscopy was used to visualize the distribution of ADAMTS5 in the urinary bladder tissue.

RESULTS: Immunoreactivity for ADAMTS5 was demonstrated in the urothelium and in the detrusor. This expression was localized not only in the cytoplasm, but also in the nuclei. Confocal microscopy corroborated these findings.

CONCLUSION: Expression of ADAMTS5 was demonstrated in the cytoplasm as well as in the nuclei of the urothelium and detrusor cells, suggesting that it may play a role at the transcriptional level.

Ort, förlag, år, upplaga, sidor
Informa Healthcare, 2018
Nyckelord
ADAMTS5, aggrecanase, confocal laser scanning microscopy, immunohistochemistry, nuclear, rat urothelium
Nationell ämneskategori
Urologi och njurmedicin
Identifikatorer
urn:nbn:se:oru:diva-64508 (URN)10.1080/21681805.2017.1422015 (DOI)000446242100011 ()29334289 (PubMedID)2-s2.0-85041138418 (Scopus ID)
Anmärkning

Funding Agencies:

Anna-Lisa and Bror Björnsson's Research Foundation  

Martha and Gustaf Ågren's Research Foundation  

Örebro University 

Tillgänglig från: 2018-01-25 Skapad: 2018-01-25 Senast uppdaterad: 2018-10-16Bibliografiskt granskad
Blanc, M., Kärrman, A., Kukučka, P., Scherbak, N. & Keiter, S. (2017). Mixture-specific gene expression in zebrafish (Danio rerio) embryos exposed to perfluorooctane sulfonic acid (PFOS), perfluorohexanoic acid (PFHxA) and 3,3′,4,4′,5-pentachlorobiphenyl (PCB126). Science of the Total Environment, 590-591, 249-257
Öppna denna publikation i ny flik eller fönster >>Mixture-specific gene expression in zebrafish (Danio rerio) embryos exposed to perfluorooctane sulfonic acid (PFOS), perfluorohexanoic acid (PFHxA) and 3,3′,4,4′,5-pentachlorobiphenyl (PCB126)
Visa övriga...
2017 (Engelska)Ingår i: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 590-591, s. 249-257Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Perfluorooctane sulfonic acid (PFOS) and 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) are persistent organic pollutants of high concern because of their environmental persistence, bioaccumulation and toxic properties. Besides, the amphiphilic properties of fluorinated compounds such as PFOS and perfluorohexanoic acid (PFHxA) suggest a role in increasing cell membrane permeability and solubilizing chemicals. The present study aimed at investigating whether PFOS and PFHxA are capable of modifying the activation of PCB126 toxicity-related pathways. For this purpose, zebrafish embryos were exposed in semi-static conditions to 7.5 μg/L of PCB126 alone, in the presence of 25 mg/L of PFOS, 15.7 mg/L of PFHxA or in the presence of both PFOS and PFHxA. Quantitative PCR was performed on embryos aged from 24 h post fertilization (hpf) to 96 hpf to investigate expression changes of genes involved in metabolism of xenobiotics (ahr2, cyp1a), oxidative stress (gpx1a, tp53), lipids metabolism (acaa2, osbpl1a), and epigenetic mechanisms (dnmt1, dnmt3ba). Cyp1a and ahr2 expression were significantly induced by the presence of PCB126. However, after 72 and 78 h of exposure, induction of cyp1a expression was significantly lower when embryos were co-exposed to PCB126 + PFOS + PFHxA when compared to PCB126-exposed embryos. Significant upregulation of gpx1a occurred after exposure to PCB126 + PFHxA and to PCB126 + PFOS + PFHxA at 30 and 48 hpf. Besides, embryos appeared more sensitive to PCB126 + PFOS + PFHxA at 78 hpf: acaa2 and osbpl1a were significantly downregulated; dnmt1 was significantly upregulated. While presented as environmentally safe, PFHxA demonstrated that it could affect gene expression patterns in zebrafish embryos when combined to PFOS and PCB126, suggesting that such mixture may increase PCB126 toxicity. This is of particular relevance since PFHxA is persistent and still being ejected into the environment. Moreover, it provides additional information as to the importance to integrate mixture effects of chemicals in risk assessment and biomonitoring frameworks.

Ort, förlag, år, upplaga, sidor
Elsevier, 2017
Nyckelord
Mixture toxicity PFAS Molecular pathway Zebrafish cyp1a Lipids
Nationell ämneskategori
Miljövetenskap Biokemi och molekylärbiologi
Forskningsämne
Miljövetenskap
Identifikatorer
urn:nbn:se:oru:diva-57792 (URN)10.1016/j.scitotenv.2017.02.232 (DOI)000399511800026 ()28283292 (PubMedID)2-s2.0-85014558344 (Scopus ID)
Anmärkning

Funding agencies:

ERASMUS program 

Tillgänglig från: 2017-05-22 Skapad: 2017-05-22 Senast uppdaterad: 2017-10-18Bibliografiskt granskad
Khalaf, H., Nakka, S. S., Sandén, C., Svärd, A., Hultenby, K., Scherbak, N., . . . Bengtsson, T. (2016). Antibacterial effects of Lactobacillus and bacteriocin PLNC8 αβ on the periodontal pathogen Porphyromonas gingivalis. BMC Microbiology, 16(1), Article ID 188.
Öppna denna publikation i ny flik eller fönster >>Antibacterial effects of Lactobacillus and bacteriocin PLNC8 αβ on the periodontal pathogen Porphyromonas gingivalis
Visa övriga...
2016 (Engelska)Ingår i: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 16, nr 1, artikel-id 188Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: The complications in healthcare systems associated with antibiotic-resistant microorganisms have resulted in an intense search for new effective antimicrobials. Attractive substances from which novel antibiotics may be developed are the bacteriocins. These naturally occurring peptides are generally considered to be safe and efficient at eliminating pathogenic bacteria. Among specific keystone pathogens in periodontitis, Porphyromonas gingivalis is considered to be the most important pathogen in the development and progression of chronic inflammatory disease. The aim of the present study was to investigate the antimicrobial effects of different Lactobacillus species and the two-peptide bacteriocin PLNC8 αβ on P. gingivalis.

Results: Growth inhibition of P. gingivalis was obtained by viable Lactobacillus and culture media from L. plantarum NC8 and 44048, but not L. brevis 30670. The two-peptide bacteriocin from L. plantarum NC8 (PLNC8 αβ) was found to be efficient against P. gingivalis through binding followed by permeabilization of the membranes, using Surface plasmon resonance analysis and DNA staining with Sytox Green. Liposomal systems were acquired to verify membrane permeabilization by PLNC8 αβ. The antimicrobial activity of PLNC8 αβ was found to be rapid (1 min) and visualized by TEM to cause cellular distortion through detachment of the outer membrane and bacterial lysis.

Conclusion: Soluble or immobilized PLNC8 αβ bacteriocins may be used to prevent P. gingivalis colonization and subsequent pathogenicity, and thus supplement the host immune system against invading pathogens associated with periodontitis.

Ort, förlag, år, upplaga, sidor
London, United Kingdom: BioMed Central, 2016
Nyckelord
Periodontitis, P. gingivalis, Lactobacillus, Bacteriocin, PLNC8
Nationell ämneskategori
Mikrobiologi
Identifikatorer
urn:nbn:se:oru:diva-51749 (URN)10.1186/s12866-016-0810-8 (DOI)000383422500001 ()27538539 (PubMedID)2-s2.0-84982308370 (Scopus ID)
Forskningsfinansiär
Hjärt-LungfondenKK-stiftelsenMagnus Bergvalls Stiftelse
Anmärkning

Funding Agency:

Foundation of Olle Engkvist

Tillgänglig från: 2016-08-23 Skapad: 2016-08-23 Senast uppdaterad: 2017-11-28Bibliografiskt granskad
Jacobsen, A., Yemaneab, B., Jass, J. & Scherbak, N. (2014). Reference gene selection for qPCR Is dependent on cell type rather than treatment in colonic and vaginal human epithelial cell lines. PLoS ONE, 9(12), e115592
Öppna denna publikation i ny flik eller fönster >>Reference gene selection for qPCR Is dependent on cell type rather than treatment in colonic and vaginal human epithelial cell lines
2014 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 12, s. e115592-Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The ability of commensal bacteria to influence gene expression in host cells under the influence of pathogenic bacteria has previously been demonstrated, however the extent of this interaction is important for understanding how bacteria can be used as probiotics. Real-time quantitative polymerase chain reaction is the most sensitive tool for evaluating relative changes to gene expression levels. However as a result of its sensitivity an appropriate method of normalisation should be used to account for any variation incurred in preparatory experimental procedures. These variations may result from differences in the amount of starting material, quality of extracted RNA, or in the efficiency of the reverse transcriptase or polymerase enzymes. Selection of an endogenous control gene is the preferred method of normalisation, and ideally a proper validation of the gene's appropriateness for the study in question should be performed. In this study we used quantitative polymerase chain reaction data and applied four different algorithms (geNorm, BestKeeper, NormFinder, and comparative ΔCq) to evaluate eleven different genes as to their suitability as endogenous controls for use in studies involving colonic (HT-29) and vaginal (VK2/E6E7) human mucosal epithelial cells treated with probiotic and pathogenic bacteria. We found phosphoglycerate kinase 1 to be most appropriate for HT-29 cells, and ribosomal protein large P0 to be the best choice for VK2/E6E7 cells. We also showed that use of less stable reference genes can lead to less accurate quantification of expression levels of gene of interest (GOI) and also can result in decreased statistical significance for GOI expression levels when compared to control. Additionally, we found the cell type being analysed had greater influence on reference gene selection than the treatment performed. This study provides recommendations for stable endogenous control genes for use in further studies involving colonic and vaginal cell lines after bacterial challenge.

Ort, förlag, år, upplaga, sidor
San Fransisco, USA: Punlic Library of Science, 2014
Nyckelord
Gene expression, lactobacillus, microbial pathogens, epithelial cells
Nationell ämneskategori
Cellbiologi
Forskningsämne
Molekylär cellbiologi
Identifikatorer
urn:nbn:se:oru:diva-39964 (URN)10.1371/journal.pone.0115592 (DOI)000347186200038 ()25526394 (PubMedID)2-s2.0-84919761377 (Scopus ID)
Forskningsfinansiär
KK-stiftelsenCarl Tryggers stiftelse för vetenskaplig forskning
Tillgänglig från: 2014-12-22 Skapad: 2014-12-22 Senast uppdaterad: 2018-11-30Bibliografiskt granskad
Krivospitskaya, O., Elmabsout, A. A., Sundman, E., Söderström, L. A., Ovchinnikova, O., Gidlöf, A. C., . . . Olofsson, P. S. (2012). A CYP26B1 polymorphism enhances retinoic acid catabolism and may aggravate atherosclerosis. Molecular medicine (Cambridge, Mass. Print), 18(1), 712-718
Öppna denna publikation i ny flik eller fönster >>A CYP26B1 polymorphism enhances retinoic acid catabolism and may aggravate atherosclerosis
Visa övriga...
2012 (Engelska)Ingår i: Molecular medicine (Cambridge, Mass. Print), ISSN 1076-1551, E-ISSN 1528-3658, Vol. 18, nr 1, s. 712-718Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

All-trans retinoic acid, controlled by CYP26 enzymes, potentially has beneficial effects in atherosclerosis treatment. This study investigates CYP26B1 in atherosclerosis and effects of a genetic polymorphism in CYP26B1 on retinoid catabolism. We found that CYP26B1 mRNA was induced by retinoic acid in human atherosclerotic arteries and CYP26B1 and the macrophage marker CD68 co-localized in human atherosclerotic lesions. In mice, Cyp26B1 mRNA was higher in atherosclerotic than normal arteries. Databases were queried for non-synonymous CYP26B1 SNPs and rs2241057 selected for further studies. Constructs of the CYP26B1 variants were created and used for production of purified proteins and transfection of macrophage-like cells. The minor variant catabolized retinoic acid with significantly higher efficiency, indicating that rs2241057 is functional and suggesting reduced retinoid availability in tissues with the minor variant. rs2241057 was investigated in a Stockholm Coronary Atherosclerosis Risk Factor (SCARF) subgroup. The minor allele was associated with slightly larger lesions as determined by angiography. In summary, this study identifies the first CYP26B1 polymorphism that alters CYP26B1 capacity to metabolize retinoic acid. CYP26B1 was expressed in macrophage-rich areas of human atherosclerotic lesions, induced by retinoic acid and increased in murine atherosclerosis. Taken together, the results indicate that CYP26B1 capacity is genetically regulated and suggest that local CYP26B1 activity may influence atherosclerosis.

Ort, förlag, år, upplaga, sidor
New York, USA: The Feinstein Institute for Medical Research, 2012
Nationell ämneskategori
Medicin och hälsovetenskap Biokemi och molekylärbiologi
Forskningsämne
Medicin
Identifikatorer
urn:nbn:se:oru:diva-23259 (URN)10.2119/molmed.2012.00094 (DOI)000306034400018 ()22415012 (PubMedID)2-s2.0-84887594213 (Scopus ID)
Forskningsfinansiär
Hjärt-LungfondenSvenska Sällskapet för Medicinsk Forskning (SSMF)Wenner-Gren Stiftelserna
Anmärkning

Funding Agencies:

Swedish Health Care Sciences Postgraduate School (NFVO) at Karolinska Institutet 

Bergwall's Foundation 

Tillgänglig från: 2012-06-05 Skapad: 2012-06-05 Senast uppdaterad: 2018-08-27Bibliografiskt granskad
Karlsson, M., Scherbak, N., Reid, G. & Jass, J. (2012). Lactobacillus rhamnosus GR-1 enhances NF-kappaB activation in Escherichia coli-stimulated urinary bladder cells through TLR4. BMC Microbiology, 12, 15
Öppna denna publikation i ny flik eller fönster >>Lactobacillus rhamnosus GR-1 enhances NF-kappaB activation in Escherichia coli-stimulated urinary bladder cells through TLR4
2012 (Engelska)Ingår i: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 12, s. 15-Artikel i tidskrift (Refereegranskat) 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.

Ort, förlag, år, upplaga, sidor
BioMed Central, 2012
Nationell ämneskategori
Mikrobiologi
Forskningsämne
Mikrobiologi; Immunologi
Identifikatorer
urn:nbn:se:oru:diva-21288 (URN)10.1186/1471-2180-12-15 (DOI)000301484000001 ()22264349 (PubMedID)2-s2.0-84856001528 (Scopus ID)
Tillgänglig från: 2012-02-17 Skapad: 2012-01-24 Senast uppdaterad: 2018-05-08Bibliografiskt granskad
Karlsson, M., Scherbak, N., Khalaf, H., Olsson, P.-E. & Jass, J. (2012). Substances released from probiotic Lactobacillus rhamnosus GR-1 potentiate NF-κB activity in Escherichia coli-stimulated urinary bladder cells. FEMS Immunology and Medical Microbiology, 66(2), 147-156
Öppna denna publikation i ny flik eller fönster >>Substances released from probiotic Lactobacillus rhamnosus GR-1 potentiate NF-κB activity in Escherichia coli-stimulated urinary bladder cells
Visa övriga...
2012 (Engelska)Ingår i: FEMS Immunology and Medical Microbiology, ISSN 0928-8244, E-ISSN 1574-695X, Vol. 66, nr 2, s. 147-156Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Lactobacillus rhamnosus GR-1 is a probiotic bacterium used to maintain urogenital health. The putative mechanism for its probiotic effect is by modulating the host immunity. Urinary tract infections (UTI) are often caused by uropathogenic Escherichia coli that frequently evade or suppress immune responses in the bladder and can target pathways, including nuclear factor-kappaB (NF-κB). We evaluated the role of L. rhamnosus GR-1 on NF-κB activation in E. coli-stimulated bladder cells. Viable L. rhamnosus GR-1 was found to potentiate NF-κB activity in E. coli-stimulated T24 bladder cells, whereas heat-killed lactobacilli demonstrated a marginal increase in NF-κB activity. Surface components released by trypsin- or LiCl treatment, or the resultant heat-killed shaved lactobacilli, had no effect on NF-κB activity. Isolation of released products from L. rhamnosus GR-1 demonstrated that the induction of NF-κB activity was owing to released product(s) with a relatively large native size. Several putative immunomodulatory proteins were identified, namely GroEL, elongation factor Tu and NLP/P60. GroEL and elongation factor Tu have previously been shown to elicit immune responses from human cells. Isolating and using immune-augmenting substances produced by lactobacilli is a novel strategy for the prevention or treatment of UTI caused by immune-evading E. coli.

Ort, förlag, år, upplaga, sidor
Hoboken, USA: Wiley-Blackwell, 2012
Nyckelord
Immune response, cytokines, lactobacilli, urothelium, uropathogen, secretome
Nationell ämneskategori
Immunologi Mikrobiologi
Forskningsämne
Biologi
Identifikatorer
urn:nbn:se:oru:diva-22594 (URN)10.1111/j.1574-695X.2012.00994.x (DOI)000310277300003 ()22620976 (PubMedID)2-s2.0-84867727218 (Scopus ID)
Anmärkning

Funding Agencies:

Knowledge Foundation

Magnus Bergvalls Foundation 

Sparbanksstiftelsen Nya 

Carl Tryggers Foundation, Sweden 

Tillgänglig från: 2012-04-19 Skapad: 2012-04-19 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
Organisationer
Identifikatorer
ORCID-id: ORCID iD iconorcid.org/0000-0001-9713-2365

Sök vidare i DiVA

Visa alla publikationer