Monireh Zare; Behnaz Valipour; Seyede Momeneh Mohammadi; Mohammad Nouri; Aliakbar Movassaghpour; Hojjatollah Nozad Charoudeh
Volume 14, Issue 3 , September 2017, , Pages 192-199
Abstract
Background: The mammalian target of rapamycin (mTOR) is important in hematopoiesis. Despite the central role of mTOR in regulating the differentiation of immune cells, the effect of mTOR function on cord blood mononuclear cells is yet to be defined. Objectives: To evaluate the effect of mTOR inhibition, ...
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Background: The mammalian target of rapamycin (mTOR) is important in hematopoiesis. Despite the central role of mTOR in regulating the differentiation of immune cells, the effect of mTOR function on cord blood mononuclear cells is yet to be defined. Objectives: To evaluate the effect of mTOR inhibition, using rapamycin on the proliferation and apoptosis of cord blood mononuclear cells, as well as on the B and T cell expansion. Methods: Cord blood mononuclear cells were cultured in the presence of IL-2, IL-7 and IL-15 cytokines and inhibited by rapamycin for 14 days. The harvested cells were evaluated at distinct time points by flow cytometry. Results: The mTOR expression decreased in the presence of rapamycin on day 14. Inhibition of mTOR reduced the proliferation of the cord blood mononuclear cells, yet did not influence apoptosis. Moreover, the number of T and NK cells was significantly reduced in the presence of rapamycin, while no change was observed in the B cell expansion. Conclusion: mTOR signaling plays a crucial part in cord blood derived NK and T cells expansion.
Mansour Salehi; Bahram Bagherpour; Vahid Shayghannejad; Farzaneh Mohebi; Rasool Jafari
Volume 13, Issue 2 , June 2016, , Pages 141-147
Abstract
Background: Management of multiple sclerosis (MS) is based on the usage of immunosuppressive and immune-modulating medications. Cytokines play an important role in the pathogenesis of MS. Objective: To evaluate the effects of rapamycin on the concentrations of Th1/Th2/Th17 serum cytokines in patients ...
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Background: Management of multiple sclerosis (MS) is based on the usage of immunosuppressive and immune-modulating medications. Cytokines play an important role in the pathogenesis of MS. Objective: To evaluate the effects of rapamycin on the concentrations of Th1/Th2/Th17 serum cytokines in patients with MS. Methods: Six patients with relapsing remitting MS as a case group and 6 healthy individuals as a control group were enrolled. The patients have been receiving 2 mg rapamycin daily for 6 months. The individuals in control group received nothing during 6 months of the experiment. Enzyme linked immunosorbent assay (Simultaneous Multi-Analyte ELISA) technique was used for determination of serum concentrations of IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, IFN-γ, TNF-α, G-CSF and TGF-β before and after therapy with rapamycin. Results: The mean absorbance of 10 out of the 12 studied cytokines showed reduction after the therapy with rapamycin including IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, IFN-γ and TNF-α. The only statistically significant reduction was observed in the absorbance of IFN-γ (p=0.028). Two cytokines illustrated increase in the patients sera after the therapy, including G-CSF and TGF-β, but only increase in TGF-β was statistically significant (p=0.046). None of the studied cytokines in the control group varied significantly after 6 months. Conclusion: Based on the findings of this study, rapamycin has some immunosuppressive effects, such as decreasing IFN-γ, which can improve the quality of life of the patients with multiple sclerosis. Also the increased level of TGF-β may also have benefits on the disease, which needs further clinical studies.