OBJECTIVE:To investigate the effects of icariin on apoptosis and the expression of Fas, Fas ligand(Fas L), B cell lymphoma(Bcl-2), and Bcl-2-associated X protein(Bax) in CD4+ T lymphocytes from patients with ankylosin...OBJECTIVE:To investigate the effects of icariin on apoptosis and the expression of Fas, Fas ligand(Fas L), B cell lymphoma(Bcl-2), and Bcl-2-associated X protein(Bax) in CD4+ T lymphocytes from patients with ankylosing spondylitis.METHODS:Primary cultures of peripheral blood CD4+ T lymphocytes were established and treated with icariin at high, medium, and low doses(0.5,0.25, and 0.125 mg/mL).Sulfasalazine treated and helthy cells were used as controls.Apoptosis of treated cells was determined by flow cytometry.Reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assays were used to determine the effects of icariin on the expression of Fas, Fas L, Bcl-2, and Bax.The activity of caspase 8 and caspase 3 was determined by a colorimetric assay.RESULTS:The m RNA and protein expression of Fas,and activity of caspase 8 and caspase 3 in CD4+ T lymphocytes were increased by icariin(P < 0.05).Conversely, the m RNA and protein expression of Bcl-2 was decreased(P < 0.05).The expression of Fas L and Bax were not significantly different between groups.The proapoptotic effects of icariin were dose-dependent.CONCLUSION:Icariin induces the apoptosis of CD4 + T cells from patients with AS comparing to normal control.Therefore, the induction of apoptosis may be the likely mechanism of action of icariin's antirheumatics activities.展开更多
CD38 is known to play roles in various inflammatory pathways.However,whether it has a protective or detrimental effect during bacterial septicemia remains disputed.Herein,this study aimed to determine the potential ef...CD38 is known to play roles in various inflammatory pathways.However,whether it has a protective or detrimental effect during bacterial septicemia remains disputed.Herein,this study aimed to determine the potential effect of CD38 on renal injury in septicemia.Escherichia coli(E.coli)was used to induce sepsis-associated renal injury in mice.WT and CD38-/-mice were stimulated with E.coli.After three hours,the serum was collected to detect renal function.Function mRNA expressions inflammatory cytokines in kidneys were quantified by real-time PCR.Hematoxylin and eosin staining were used to observe the histomorphology of kidney.The expression of TLR4,NF-κB,MAPK and cytokines were detected by Western Blot.Our results demonstrated that 3×10^(8) cfu/mL E.coli is the appropriate dose to induce sepsis mice model.Compared to WT sepsis mice,CD38-/-mice showed aggravated kidney injuries with impaired renal function,increased inflammation and apoptosis after E.coli stimulation.Interestingly,CD38 deficiency also led to elevated expression of TLR4 and increased phosphorylation of NF-κB p65/p105 and ERK1/2.To sum up,our results suggested that CD38 deficiency could aggravate E.coli-induced renal injury through activating ERK1/2-NF-κB signaling pathway.展开更多
基金Supported by the Fundamental Research Funds for the Central Public Welfare Research Institutes:Pharmacogenomics of Tripterygium wilfordii Hook F response and liver toxic reaction in Rheumatoid Arthritis(No.ZZ0708079)the Fundamental Research Funds for the Central Public Welfare Research Institutes Pharmacogenomics of Tripterygium wilfordii Hook F response reaction in Rheumatoid Arthritis(No.31470962)
文摘OBJECTIVE:To investigate the effects of icariin on apoptosis and the expression of Fas, Fas ligand(Fas L), B cell lymphoma(Bcl-2), and Bcl-2-associated X protein(Bax) in CD4+ T lymphocytes from patients with ankylosing spondylitis.METHODS:Primary cultures of peripheral blood CD4+ T lymphocytes were established and treated with icariin at high, medium, and low doses(0.5,0.25, and 0.125 mg/mL).Sulfasalazine treated and helthy cells were used as controls.Apoptosis of treated cells was determined by flow cytometry.Reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assays were used to determine the effects of icariin on the expression of Fas, Fas L, Bcl-2, and Bax.The activity of caspase 8 and caspase 3 was determined by a colorimetric assay.RESULTS:The m RNA and protein expression of Fas,and activity of caspase 8 and caspase 3 in CD4+ T lymphocytes were increased by icariin(P < 0.05).Conversely, the m RNA and protein expression of Bcl-2 was decreased(P < 0.05).The expression of Fas L and Bax were not significantly different between groups.The proapoptotic effects of icariin were dose-dependent.CONCLUSION:Icariin induces the apoptosis of CD4 + T cells from patients with AS comparing to normal control.Therefore, the induction of apoptosis may be the likely mechanism of action of icariin's antirheumatics activities.
基金supported by the National Natural Sciences Foundation of China (NSFC) grant numbers [31960165&81760288]
文摘CD38 is known to play roles in various inflammatory pathways.However,whether it has a protective or detrimental effect during bacterial septicemia remains disputed.Herein,this study aimed to determine the potential effect of CD38 on renal injury in septicemia.Escherichia coli(E.coli)was used to induce sepsis-associated renal injury in mice.WT and CD38-/-mice were stimulated with E.coli.After three hours,the serum was collected to detect renal function.Function mRNA expressions inflammatory cytokines in kidneys were quantified by real-time PCR.Hematoxylin and eosin staining were used to observe the histomorphology of kidney.The expression of TLR4,NF-κB,MAPK and cytokines were detected by Western Blot.Our results demonstrated that 3×10^(8) cfu/mL E.coli is the appropriate dose to induce sepsis mice model.Compared to WT sepsis mice,CD38-/-mice showed aggravated kidney injuries with impaired renal function,increased inflammation and apoptosis after E.coli stimulation.Interestingly,CD38 deficiency also led to elevated expression of TLR4 and increased phosphorylation of NF-κB p65/p105 and ERK1/2.To sum up,our results suggested that CD38 deficiency could aggravate E.coli-induced renal injury through activating ERK1/2-NF-κB signaling pathway.
