- METHODS. OFs and T cells were derived from GO patients and healthy control (Ctl) persons. S1P abundance in orbital tissues was evaluated by immunofluorescence. OFs were stimulated with CD40 ligand and S1P levels were determined by ELISA. Further, activities of acid sphingomyelinase (ASM), acid ceramidase, and sphingosine kinase were measured by ultraperformance liquid chromatography. Sphingosine and ceramide contents were analyzed by mass spectrometry. Finally, the role for S1P in T-cell attraction was investigated by T-cell migration assays. RESULTS. GO orbital tissue showed elevated amounts of S1P as compared to control samples. Stimulation of CD40 induced S1P expression in GO-derived OFs, while Ctl-OFs remained unaffected. A significant increase of ASM and sphingosine kinase activities, as well as lipid formation, was observed in GO-derived OFs. Migration assay of T cells in the presence of SphK inhibitor revealed that S1P released by GO-OFs attracted T cells for migration. CONCLUSIONS. The results demonstrated that CD40 ligandMETHODS. OFs and T cells were derived from GO patients and healthy control (Ctl) persons. S1P abundance in orbital tissues was evaluated by immunofluorescence. OFs were stimulated with CD40 ligand and S1P levels were determined by ELISA. Further, activities of acid sphingomyelinase (ASM), acid ceramidase, and sphingosine kinase were measured by ultraperformance liquid chromatography. Sphingosine and ceramide contents were analyzed by mass spectrometry. Finally, the role for S1P in T-cell attraction was investigated by T-cell migration assays. RESULTS. GO orbital tissue showed elevated amounts of S1P as compared to control samples. Stimulation of CD40 induced S1P expression in GO-derived OFs, while Ctl-OFs remained unaffected. A significant increase of ASM and sphingosine kinase activities, as well as lipid formation, was observed in GO-derived OFs. Migration assay of T cells in the presence of SphK inhibitor revealed that S1P released by GO-OFs attracted T cells for migration. CONCLUSIONS. The results demonstrated that CD40 ligand stimulates GO fibroblast to produce S1P, which is a driving force for T-cell migration. The results support the use of S1P receptor signaling modulators in GO management.…
MetadatenAuthor details: | Svenja PlöhnGND, Bärbel EdelmannGND, Lukasz JaptokGND, Xingxuan He, Matthias HoseGND, Wiebke HansenGND, Edward H. Schuchman, Anja Eckstein, Utta Berchner-PfannschmidtGND |
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DOI: | https://doi.org/10.1167/iovs.18-25466 |
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ISSN: | 0146-0404 |
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ISSN: | 1552-5783 |
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Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/30452592 |
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Title of parent work (English): | Investigative ophthalmology & visual science |
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Subtitle (English): | potential role of sphingosine-1-phosphate in inflammatory T-Cell migration in graves' orbitopathy |
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Publisher: | Association for Research in Vision and Opthalmology |
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Place of publishing: | Rockville |
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Publication type: | Article |
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Language: | English |
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Year of first publication: | 2018 |
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Publication year: | 2018 |
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Release date: | 2021/07/08 |
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Tag: | inflammation |
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Volume: | 59 |
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Issue: | 13 |
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Number of pages: | 7 |
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First page: | 5391 |
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Last Page: | 5397 |
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Funding institution: | Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [DFG GRK 2098] |
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Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft |
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DDC classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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License (German): | CC-BY-NC-ND - Namensnennung, nicht kommerziell, keine Bearbeitungen 4.0 International |
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External remark: | Zweitveröffentlichung in der Schriftenreihe Postprints der Universität Potsdam : Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe ; 1099 |
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