دورية أكاديمية
Effect of Rapamycin on MOG-Reactive Immune Cells and Lipopolysaccharide-Activated Microglia: An In Vitro Approach for Screening New Therapies for Multiple Sclerosis.
| العنوان: | Effect of Rapamycin on MOG-Reactive Immune Cells and Lipopolysaccharide-Activated Microglia: An In Vitro Approach for Screening New Therapies for Multiple Sclerosis. |
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| المؤلفون: | Borim PA; Graduate Program in Tropical Diseases, Botucatu Medical School, São Paulo State University (UNESP), Botucatu, Brazil., Mimura LAN; Institute of Biosciences, São Paulo State University (UNESP), Botucatu, Brazil., Zorzella-Pezavento SFG; Institute of Biosciences, São Paulo State University (UNESP), Botucatu, Brazil., Polonio CM; Institute of Biomedical Sciences, University of São Paulo (ICB IV/USP), São Paulo, Brazil., Peron JPS; Institute of Biomedical Sciences, University of São Paulo (ICB IV/USP), São Paulo, Brazil., Sartori A; Graduate Program in Tropical Diseases, Botucatu Medical School, São Paulo State University (UNESP), Botucatu, Brazil.; Institute of Biosciences, São Paulo State University (UNESP), Botucatu, Brazil., Fraga-Silva TFC; Graduate Program in Tropical Diseases, Botucatu Medical School, São Paulo State University (UNESP), Botucatu, Brazil. |
| المصدر: | Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research [J Interferon Cytokine Res] 2022 Apr; Vol. 42 (4), pp. 153-160. Date of Electronic Publication: 2022 Apr 06. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Mary Ann Liebert Country of Publication: United States NLM ID: 9507088 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-7465 (Electronic) Linking ISSN: 10799907 NLM ISO Abbreviation: J Interferon Cytokine Res Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Larchmont, NY : Mary Ann Liebert Original Publication: New York, NY : Mary Ann Liebert, c1995- |
| مواضيع طبية MeSH: | Encephalomyelitis, Autoimmune, Experimental*/drug therapy , Encephalomyelitis, Autoimmune, Experimental*/metabolism , Multiple Sclerosis*, Animals ; Cytokines/metabolism ; Lipopolysaccharides/pharmacology ; Mice ; Mice, Inbred C57BL ; Microglia/metabolism ; Microglia/pathology ; Peptide Fragments/metabolism ; Peptide Fragments/pharmacology ; Sirolimus/metabolism ; Sirolimus/pharmacology ; Sirolimus/therapeutic use ; Tumor Necrosis Factor-alpha/metabolism |
| مستخلص: | Rapamycin is an immunomodulatory drug that has been evaluated in preclinical and clinical trials as a disease-modifying therapy for multiple sclerosis (MS). In this study, we evaluated the in vitro effect of rapamycin on immune cells pivotally involved in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), which is an animal model to study MS. Splenocytes and central nervous system (CNS)-mononuclear cells obtained from EAE mice were stimulated with a myelin oligodendrocyte glycoprotein peptide, whereas the microglial BV-2 cell line was activated with LPS. The 3 immune cell types were simultaneously treated with rapamycin, incubated, and then used to analyze cytokines, transcription factors, and activation markers. Rapamycin reduced IL-17 production, TBX21 , and RORc expression by splenic and CNS cell cultures. IFN-γ and TNF-α production were also decreased in CNS cultures. This treatment also decreased TNF-α, IL-6, MHC II, CD40, and CD86 expression by BV-2 cells. These results indicated that in vivo immunomodulatory activity of rapamycin in MS and EAE was, in many aspects, reproduced by in vitro assays done with cells derived from the spleen and the CNS of EAE mice. This procedure could constitute a screening strategy for choosing drugs with therapeutic potential for MS. |
| فهرسة مساهمة: | Keywords: encephalomyelitis; mTOR; microglia; neuroinflammation; rapamycin |
| المشرفين على المادة: | 0 (Cytokines) 0 (Lipopolysaccharides) 0 (Peptide Fragments) 0 (Tumor Necrosis Factor-alpha) W36ZG6FT64 (Sirolimus) |
| تواريخ الأحداث: | Date Created: 20220406 Date Completed: 20220421 Latest Revision: 20220624 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1089/jir.2021.0206 |
| PMID: | 35384725 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1557-7465 |
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| DOI: | 10.1089/jir.2021.0206 |