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[Rapamycin alleviates inflammation by up-regulating TGF-β/Smad signaling in a mouse model of autoimmune encephalomyelitis].
- Source :
-
Nan fang yi ke da xue xue bao = Journal of Southern Medical University [Nan Fang Yi Ke Da Xue Xue Bao] 2019 Jan 30; Vol. 39 (1), pp. 35-42. - Publication Year :
- 2019
-
Abstract
- Objective: To evaluate the efficacy of rapmycin for treatment of experimental autoimmune encephalomyelitis (EAE) in mice and explore the underlying mechanism.<br />Methods: An EAE model was established in C57BL/6 mice. After immunization, the mice were divided into model group and rapamycin groups treated daily with low-dose (0.3 mg/kg) or high-dose (1 mg/kg) rapamycin. The clinical scores of the mice were observed using Knoz score, the infiltration of IL-17 cells in the central nervous system (CNS) was determined using immunohistochemistry; the differentiation of peripheral Treg cells was analyzed using flow cytometry, and the changes in the levels of cytokines were detected with ELISA; the changes in the expressions of p-Smad2 and p- smad3 were investigated using Western blotting.<br />Results: High-dose rapamycin significantly improved the neurological deficits scores of EAE mice. In high-dose rapamycin group, the scores in the onset stage, peak stage and remission stage were 0.14±0.38, 0.43±1.13 and 0.14±0.37, respectively, as compared with 1.14±0.69, 2.14±1.06 and 2.2±0.75 in the model group. The infiltration of inflammatory IL-17 cells was significantly lower in high-dose rapamycin group than in the model group (43±1.83 vs 153.5±7.02). High-dose rapamycin obviously inhibited the production of IL-12, IFN-γ, IL-17 and IL-23 and induced the anti-inflammatory cytokines IL-10 and TGF-β. The percentage of Treg in CD4+ T cells was significantly higher in high- dose rapamycin group than in the model group (10.17 ± 0.68 vs 3.52 ± 0.32). In the in vitro experiment, combined treatments of the lymphocytes isolated from the mice with rapamycin and TGF-β induced a significant increase in the number of Treg cells (13.66±1.89) compared with the treatment with rapamycin (6.23±0.80) or TGF-β (4.87±0.85) alone. Rapamycin also obviously up-regulated the expression of p-Smad2 and p-Smad3 in the lymphocytes.<br />Conclusions: Rapamycin can promote the differentiation of Treg cells by up-regulating the expression of p-Smad2 and p-smad3 to improve neurological deficits in mice with EAE.
- Subjects :
- Animals
Anti-Inflammatory Agents administration & dosage
Interferon-gamma metabolism
Interleukins metabolism
Lymphocytes cytology
Mice
Mice, Inbred C57BL
Sirolimus administration & dosage
T-Lymphocytes, Regulatory drug effects
Anti-Inflammatory Agents therapeutic use
Cell Differentiation drug effects
Encephalomyelitis, Autoimmune, Experimental drug therapy
Encephalomyelitis, Autoimmune, Experimental metabolism
Sirolimus therapeutic use
Smad Proteins metabolism
T-Lymphocytes, Regulatory cytology
Transforming Growth Factor beta metabolism
Up-Regulation
Subjects
Details
- Language :
- Chinese
- ISSN :
- 1673-4254
- Volume :
- 39
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nan fang yi ke da xue xue bao = Journal of Southern Medical University
- Publication Type :
- Academic Journal
- Accession number :
- 30692064
- Full Text :
- https://doi.org/10.12122/j.issn.1673-4254.2019.01.06