Background:Dermatomyositis(DM)and polymyositis(PM)are common inflammatory myopathies whose immunopathogenic mechanisms remain poorly understood.The NOD-like receptor family,pyrin domain containing 3(NLRP3)inflammasome...Background:Dermatomyositis(DM)and polymyositis(PM)are common inflammatory myopathies whose immunopathogenic mechanisms remain poorly understood.The NOD-like receptor family,pyrin domain containing 3(NLRP3)inflammasome is a type of cytoplasmic multiprotein inflammasome and is responsible for the activation of inflammatory reactivations.Responding to a wide range of exogenous and endogenous microbial or sterile stimuli,NLRP3 inflammasomes can cleave pro-caspase-1 into active caspase-1,which processes the pro-infammatory cytokines pro-interleukin(IL)-1βand pro-IL-18 into active and secreted IL-1βand I L-18.The NLRP3 inflammasome is implicated in infectious and sterile inflammatory diseases.However,it remains unclear whether it is involved in the pathogenesis of DM/PM,which we aim to address in our research.Methods:In this study,22 DM/PM patients and 24 controls were recruited.The protein and RNA expression of IL-113,IL-18,NLRP3,and caspase-1 in serum and muscle samples were tested and compared between the two groups.Results:The serum IL-1βand IL-18 levels were significantly higher in DM/PM patients than those in the controls by enzyme linked immunosorbent assay(EL1SA,DM vs.control,25.02±8.29 ng/ml vs.16.49±3.30 ng/ml,P〈0.001;PM vs.control,26.49±7.79 ng/ml vs.16.49±3.30 ng/ml,P〈0.001).Moreover,the real-time quantitative reverse transcription-polymerase chain reaction(qRT-PCR)showed that DM/PM patients exhibited higher RNA expression of IL-lβ,IL-18,and NLRP3 in the muscle(for IL-1β,DM vs.control,P 0.0012,PM vs.control,P=0.0021;for IL-18,DM vs.control,P=0.0045,PM vs.control,P 0.0031;for NLRP3,DM vs.control,P=0.0017,PM vs.control,P 0.0006).Moreover,the protein expression of NLRP3 and caspase-1 in muscle samples of DM/PM patients were also significantly elevated compared to that in the muscles of the controls.Conclusions:Our findings demonstrate that the NLRP3 inflammasome is implicated in the pathogenesis of DM/PM.High NLRP3 expression led to elevated levels of IL-l13 and IL-18 and could be one of the factors promoting disease progress.展开更多
基金This work was supported by a grant from the National Natural Science Foundation of China(No.81271399).
文摘Background:Dermatomyositis(DM)and polymyositis(PM)are common inflammatory myopathies whose immunopathogenic mechanisms remain poorly understood.The NOD-like receptor family,pyrin domain containing 3(NLRP3)inflammasome is a type of cytoplasmic multiprotein inflammasome and is responsible for the activation of inflammatory reactivations.Responding to a wide range of exogenous and endogenous microbial or sterile stimuli,NLRP3 inflammasomes can cleave pro-caspase-1 into active caspase-1,which processes the pro-infammatory cytokines pro-interleukin(IL)-1βand pro-IL-18 into active and secreted IL-1βand I L-18.The NLRP3 inflammasome is implicated in infectious and sterile inflammatory diseases.However,it remains unclear whether it is involved in the pathogenesis of DM/PM,which we aim to address in our research.Methods:In this study,22 DM/PM patients and 24 controls were recruited.The protein and RNA expression of IL-113,IL-18,NLRP3,and caspase-1 in serum and muscle samples were tested and compared between the two groups.Results:The serum IL-1βand IL-18 levels were significantly higher in DM/PM patients than those in the controls by enzyme linked immunosorbent assay(EL1SA,DM vs.control,25.02±8.29 ng/ml vs.16.49±3.30 ng/ml,P〈0.001;PM vs.control,26.49±7.79 ng/ml vs.16.49±3.30 ng/ml,P〈0.001).Moreover,the real-time quantitative reverse transcription-polymerase chain reaction(qRT-PCR)showed that DM/PM patients exhibited higher RNA expression of IL-lβ,IL-18,and NLRP3 in the muscle(for IL-1β,DM vs.control,P 0.0012,PM vs.control,P=0.0021;for IL-18,DM vs.control,P=0.0045,PM vs.control,P 0.0031;for NLRP3,DM vs.control,P=0.0017,PM vs.control,P 0.0006).Moreover,the protein expression of NLRP3 and caspase-1 in muscle samples of DM/PM patients were also significantly elevated compared to that in the muscles of the controls.Conclusions:Our findings demonstrate that the NLRP3 inflammasome is implicated in the pathogenesis of DM/PM.High NLRP3 expression led to elevated levels of IL-l13 and IL-18 and could be one of the factors promoting disease progress.
