10,11-Dehydrocurvularin(DCV)is a natural-product macrolide that has been shown to exert anti-inflammatory activity.However,the underlying mechanism of its anti-inflammatory activity remains poorly understood.Aberrant ...10,11-Dehydrocurvularin(DCV)is a natural-product macrolide that has been shown to exert anti-inflammatory activity.However,the underlying mechanism of its anti-inflammatory activity remains poorly understood.Aberrant activation of the NLRP3 inflammasome is involved in diverse inflammation-related diseases,which should be controlled.The results showed that DCV specifically inhibited the activation of the NLRP3 inflammasome in association with reduced IL-1βsecretion and caspase-1 activation,without effect on the NLRC4 and AIM2 inflammasomes.Furthermore,DCV disturbed the interaction between NEK7 and NLRP3,resulting in the inhibition of NLRP3 inflammasome activation.The C=C double bond of DCV was required for the NLRP3 inflammasome inhibition induced by DCV.Importantly,DCV ameliorated inflammation in vivo through inhibiting the NLRP3 inflammasome.Taken together,our study reveals a novel mechanism by which DCV suppresses inflammation,which indicates the potential role of DCV in NLRP3 inflammasome-driven inflammatory disorders.展开更多
基金the National Natural Science Foundation of China(No.81902852)China Postdoctoral Science Foundation(No.2020M670220)+2 种基金the Natural Science Foundation of Hubei Province of China(No.2022CFB481)the Natural Science Foundation of Hubei Provincial Department of Education(No.T2022021)Wudang Local Chinese Medicine Research of Hubei University of Medicine(No.WDCM2020004).
文摘10,11-Dehydrocurvularin(DCV)is a natural-product macrolide that has been shown to exert anti-inflammatory activity.However,the underlying mechanism of its anti-inflammatory activity remains poorly understood.Aberrant activation of the NLRP3 inflammasome is involved in diverse inflammation-related diseases,which should be controlled.The results showed that DCV specifically inhibited the activation of the NLRP3 inflammasome in association with reduced IL-1βsecretion and caspase-1 activation,without effect on the NLRC4 and AIM2 inflammasomes.Furthermore,DCV disturbed the interaction between NEK7 and NLRP3,resulting in the inhibition of NLRP3 inflammasome activation.The C=C double bond of DCV was required for the NLRP3 inflammasome inhibition induced by DCV.Importantly,DCV ameliorated inflammation in vivo through inhibiting the NLRP3 inflammasome.Taken together,our study reveals a novel mechanism by which DCV suppresses inflammation,which indicates the potential role of DCV in NLRP3 inflammasome-driven inflammatory disorders.
