Mycophenolic acid inhibits SLE-associated cytokine expression and promotes apoptosis of peripheral b

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:gegengwang
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Aim:To investigate the effect of the novel immunosuppressant mycophenolicacid(MPA)on cytokine production and apoptosis of the peripheral blood mono-nuclear cells(PBMC)of patients with systemic lupus erythematosus(SLE).Methods:The levels of IL-10,IL-12,IFN-γ,sFas and sFasL in the supernatants ofcultured PBMC from 41 SLE patients was determined by the ABC-ELISA method.The percentage of IFN-γIL- 10~-,IFN-γ-IL-10~+,and IFN-γ~+IL-10~+ subsets in CD4~+ceils were detected by three-color flow cytometry.The percentage of apoptoticTh cells was detected by AV-FITC/PI flow cytometry.Samples from 22 sex-andage-comparable healthy people were used as normal controls.Results:The lev-els of IL-10,IL-12,and IFN-γwere all significantly elevated in the supernatants ofcultured PBMC from SLE samples,compared with normal controls.The enhancedproductions of IL-10,IL-12,and IFN-γ by PBMC from SLE both spontaneouslyand stimulated by phytohaemagglutinin(PHA)were significantly reduced by MPA.The percentages of CD4+IFN-γIL-10~+ and CD4+IFN-γ~+IL-10~+ cell subsets in cul-tured PBMC from SLE were significantly increased,but decreased when MPA wasadded into the culture.After being cultured in vitro for 48h,the PBMC of SLEpatients showed a higher secretion of sFasL as well as a higher percentage ofapoptosis.MPA significantly increased the apoptotic percentage of SLE PBMC,but reduced the secretion of sFasL and sFas.Conclusion:MPA reduces theabnormal production of SLE-associated cytokines,such as IL-10,IL-12,and IFN-γ,inhibits the increase of CD4+IFN-γ~+IL-10,CD4+IFN-γIL-10~+ and CD4+IFN-γ~+IL-10~+ subset;and promotes the apoptosis of PBMC in SLE patients,which may beassociated with the therapeutic mechanism of MPA for SLE. Aim: To investigate the effect of the novel immunosuppressant mycophenolic acid (MPA) on cytokine production and apoptosis of the peripheral blood mono-nuclear cells (PBMC) of patients with systemic lupus erythematosus (SLE). Methods: The levels of IL-10, IL -12, IFN-γ, sFas and sFasL in the supernatants of cultured PBMC from 41 SLE patients was determined by the ABC-ELISA method. The percentage of IFN-γ IL-10 ~, IFN- γ-IL-10 ~ IFN-γ ~ + IL-10 ~ + subsets in CD4 ~ + ceils were detected by three-color flow cytometry. The percentage of apoptotic Th cells was detected by AV-FITC / PI flow cytometry. Samples from 22 sex-andage-comparable healthy people were used as normal controls. Results: The lev-els of IL-10, IL-12, and IFN-γwere all significantly elevated in the supernatants of cultured PBMC from SLE samples, compared with normal controls. IL-12, and IFN-γ by PBMC from SLE both spontaneously and stimulated by phytohaemagglutinin (PHA) were significantly reduced by MPA.The percentages of CD4 + IFN-γ IL-10 ~ + CD4 + IFN-γ ~ + IL-10 ~ + cell subsets in cul-tured PBMC from SLE were significantly increased, but decreased decreased when MPA was incorporated into the culture. for 48h, the PBMC of SLEpatients showed a higher secretion of sFasL as well as a higher percentage of apoptosis. MPA significantly increased the apoptotic percentage of SLE PBMC, but reduced the secretion of sFasL and sFas.Conclusion: MPA reduces theabnormal production of SLE-associated cytokines, such as IL-10, IL-12, and IFN-γ, inhibits the increase of CD4 + IFN- γ ~ + IL-10, CD4 + IFN- γIL- 10 ~ + and CD4 + IFN- γ ~ + IL -10 ~ + subset; and promotes the apoptosis of PBMC in SLE patients, which may be associated with the therapeutic mechanism of MPA for SLE.
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