Dendritic cells (DCs) are the most potent antigen-presen ting cells that play crucial roles in the regulation of immune response. Triptol ide, an active component purified from the medicinal plant Tripterygium wilfor ...Dendritic cells (DCs) are the most potent antigen-presen ting cells that play crucial roles in the regulation of immune response. Triptol ide, an active component purified from the medicinal plant Tripterygium wilfor dii Hook F., has been demonstrated to act as a potent immunosuppressive drug c apab le of inhibiting T cell activation and proliferation. However, little is known a bout the effects of triptolide on DCs. The present study shows that triptolide d oes not affect phenotypic differentiation and LPS-induced maturation of murine DCs. But triptolide can dramatically reduce cell recovery by inducing apoptosis of DCs at concentration as low as 10 ng/ml, as demonstrated by phosphatidylserin e exposure, mitochondria potential decrease, and nuclear DNA condensation. Tript olide induces activation of p38 in DCs, which precedes the activation of caspase 3. SB203580, a specific kinase inhibitor for p38, can block the activation of caspase 3 and inhibit the resultant apoptosis of DCs. Our results suggest that t he anti-inflammatory and immunosuppressive activities of triptolide may be due, in part, to its apoptosis-inducing effects on DCs.展开更多
Apoptosis is an important process for organism development that functions to eliminate cell damage,maintain homeostasis,and remove obsolete tissues during morphogenesis.In mammals,apoptosis is accompanied by the relea...Apoptosis is an important process for organism development that functions to eliminate cell damage,maintain homeostasis,and remove obsolete tissues during morphogenesis.In mammals,apoptosis is accompanied by the release of cytochrome C(Cyt-c)from mitochondria to the cytoplasm.However,whether this process is conserved in the fruit fly,Drosophila melanogaster,remains controversial.In this study,we discovered that during the degradation of Drosophila salivary gland,the transcription of mitochondria apoptosis factors(MAPFs),Cyt-c,and death-associated APAF1-related killer(Dark)encoding genes are all upregulated antecedent to initiator and effector caspases encoding genes.The proteins Cyt-c and the active caspase 3 appear gradually in the cytoplasm during salivary gland degradation.Meanwhile,the Cyt-c protein colocates with mito-GFP,the marker indicating cytoplasmic mitochondria,and the change in mitochondrial membrane potential coincides with the appearance of Cyt-c in the cytoplasm.Moreover,impeding or promoting 20E-induced transcription factor E93 suppresses or enhances the staining of Cyt-c and the active caspase 3 in the cytoplasm of salivary gland,and accordingly decreases or increases the mitochondrial membrane potential,respectively.Our research provides evidence that cytoplasmic Cyt-c appears before apoptosis during Drosophila salivary gland degradation,shedding light on partial conserved mechanism in apoptosis between insects and mammals.展开更多
文摘Dendritic cells (DCs) are the most potent antigen-presen ting cells that play crucial roles in the regulation of immune response. Triptol ide, an active component purified from the medicinal plant Tripterygium wilfor dii Hook F., has been demonstrated to act as a potent immunosuppressive drug c apab le of inhibiting T cell activation and proliferation. However, little is known a bout the effects of triptolide on DCs. The present study shows that triptolide d oes not affect phenotypic differentiation and LPS-induced maturation of murine DCs. But triptolide can dramatically reduce cell recovery by inducing apoptosis of DCs at concentration as low as 10 ng/ml, as demonstrated by phosphatidylserin e exposure, mitochondria potential decrease, and nuclear DNA condensation. Tript olide induces activation of p38 in DCs, which precedes the activation of caspase 3. SB203580, a specific kinase inhibitor for p38, can block the activation of caspase 3 and inhibit the resultant apoptosis of DCs. Our results suggest that t he anti-inflammatory and immunosuppressive activities of triptolide may be due, in part, to its apoptosis-inducing effects on DCs.
基金This study was supported by Laboratory of Lingnan Modern Agriculture Project(NT2021003 to S.Li)the National Natural Science Foundation of China(Grants No.32070491 to K.Li and 31900355 to N.Li)the National Science Foundation of Guangdong Province(Grants No.2022A1515010457 to K.Li and 2022A1515011759 to N.Li).English was edited by the Nature Publishing Group.
文摘Apoptosis is an important process for organism development that functions to eliminate cell damage,maintain homeostasis,and remove obsolete tissues during morphogenesis.In mammals,apoptosis is accompanied by the release of cytochrome C(Cyt-c)from mitochondria to the cytoplasm.However,whether this process is conserved in the fruit fly,Drosophila melanogaster,remains controversial.In this study,we discovered that during the degradation of Drosophila salivary gland,the transcription of mitochondria apoptosis factors(MAPFs),Cyt-c,and death-associated APAF1-related killer(Dark)encoding genes are all upregulated antecedent to initiator and effector caspases encoding genes.The proteins Cyt-c and the active caspase 3 appear gradually in the cytoplasm during salivary gland degradation.Meanwhile,the Cyt-c protein colocates with mito-GFP,the marker indicating cytoplasmic mitochondria,and the change in mitochondrial membrane potential coincides with the appearance of Cyt-c in the cytoplasm.Moreover,impeding or promoting 20E-induced transcription factor E93 suppresses or enhances the staining of Cyt-c and the active caspase 3 in the cytoplasm of salivary gland,and accordingly decreases or increases the mitochondrial membrane potential,respectively.Our research provides evidence that cytoplasmic Cyt-c appears before apoptosis during Drosophila salivary gland degradation,shedding light on partial conserved mechanism in apoptosis between insects and mammals.
