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Cytokine expression in human endothelial cells stimulated with clinical isolates and culture filtrate of Staphylococcus aureus
Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
Department of Microbiology, Hospital of Ryhov, Jönköping.
Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Human umbilical vein endothelial cells (HUVEC) were infected for 24 h with 18 well-characterized, noninvasive Staphylococcus aureus isolates and the supernatants were analyzed for IL-1ß, TNF-α, IL-6, IL-8, IL-10, IL-12p70, GRO-α, GM-CSF and RANTES by immuno assay. All isolates induced expression of IL-6, IL-8, GRO-α, GM-CSF, and RANTES. The highest concentrations were observed for IL-6, IL-8 and GRO-α, which reached levels close to that of HUVEC stimulated with LPS (0.1µg ml-1). The magnitude of cytokine expression varied between isolates. S. aureus inducing high expression of one of these cytokines also showed simultaneous high expression of the other four, indicating a common ability of individual S. aureus to induce high or low expression of these cytokines. IL-1ß, TNF-α, IL-10 and IL-12p70 were not upregulated by any of the S. aureus isolates. No correlation between cytokine profile and S. aureus production of enterotoxin A-D, TSST-1, cytotoxicity, PFGE and phage pattem or susceptibility to methicillin was observed. The ability of individual S. aureus to induce expression of cytokines correlated with their ability to upregulate ICAM-1, but not E-selectin, in HUVEC. Similarly, a heat-stable, high molecular weight component(s) from sterile culture filtrate of S. aureus upregulated expression of IL-8 and ICAM-1 in HUVEC.

Our results show that individual clinical isolates of S. aureus vary in ability to directly stimulate human endothelial cells to upregulate cytoldnes that promote leukocyte recruitment and inflammation.

National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-84631OAI: oai:DiVA.org:liu-84631DiVA: diva2:560856
Available from: 2012-10-16 Created: 2012-10-16 Last updated: 2012-10-16Bibliographically approved
In thesis
1. Innate immune response in human endothelial cells: characterization and regulation of E-selectin, ICAM-I and cytokine expression and the role of Staphylococcus aureus
Open this publication in new window or tab >>Innate immune response in human endothelial cells: characterization and regulation of E-selectin, ICAM-I and cytokine expression and the role of Staphylococcus aureus
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Endothelial cells located on the vessel walls play an important role in inflammation. In response to cytokines or other inflammatory mediators such as microorganisms, endothelial cells express cell adhesion molecules such as E-selectin and ICAM-1 that are involved in binding circulating leukocytes to the endothelium. Since E-selectin is highly glycosylated one aim of this thesis was to investigate the role of N-glycosylation in E-selectin expression and function. Modification of glycosylation was obtained by culturing HUVEC in the presence of soluble glycosylation inhibitors. The result showed that E-selectin is highly glycosylated with N-Iinked, complex type oligosaccharides which were found to be important for the level of cell surface expression and turnover time. However, defect glycosylation did not affect its binding properties as revealed in a static cell-binding assay. Combinations of cytokines can produce a different expression of E-selectin. When TNF-α and IFN-γ were used to stimulate HUVEC an enhanced and prolonged expression of E-selectin was obtained compared to when HUVEC were stimulated with TNF-α alone. This effect could be blocked by monensin, which is an inhibitor of trans-Golgi network processing. This again indicated a role for posttranslational modification in regulation of E-selectin expression.

Eighteen clinical isolates of Staphylococcus aureus were analysed for their ability to induce expression of E-selectin and ICAM-1 in HUVEC. Upregulation of adhesion molecules varied between isolates; 17 isolates induced expression of E-selectin and 13 of ICAM-1. Some isolates induced a significant expression of E-selectin without stimulation of ICAM-1, whereas the opposite was not found. Bacterial viability was required for induction of the adhesion molecules. There was no correlation between ability of S. aureus to induce expression of cell adhesion molecules and methicillin susceptibility, pulse field electrophoresis patterns, biochemical characteristics, phage typing or toxin production. Nine cytokines, IL-1ß, TNF-α, IL-6, IL-8, IL-10, IL-12p70, GRO-α, GM-CSF and RANTES, all of importance in the inflammatory process, were analysed in supernatants from HUVEC stimulated with eighteen isolates of S. aureus. All isolates induced IL-6, IL-8, GRO-α, GM-CSF and RANTES. Isolates of S. aureus inducing high expression of one of these cytokines also showed high expression of the other four, indicating a possible common mechanism for regulation of the expression of these cytokines. The ability of individual S. aureus isolates to induce expression of cytokines correlated with their ability to induce expression of ICAM-1 but not E-selectin in HUVEC. No correlation between cytokine profile and S. aureus production of enterotoxin A-D, TSST-1, cytotoxicity, PFGE- and phage pattern or susceptibility to methicillin was observed. Furthermore, culture filtrate from S. aureus induced expression of ICAM-1 and IL-8 in HUVEC. The component(s) from culture filtrates were heat-stable, had a molecular weight of about 100 kDa and the effect was independent of the presence of fetal calf serum in media.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2003. 52 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 804
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-26669 (URN)11235 (Local ID)91-7373-493-4 (ISBN)11235 (Archive number)11235 (OAI)
Public defence
2003-09-26, Elsa Brändströmsalen, Hälsouniversitet, Linköping, 13:00 (Swedish)
Opponent
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-10-16Bibliographically approved

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Strindhall, JanLindgren, Per-EricKihlström, Erik

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