论文部分内容阅读
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-inflammatory cytokines pro-interleukin (IL)-1 β and pro-IL-18 into active and secreted IL-1 β and IL-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-1β,IL-18,NLRP3,and caspase-1 in serum and muscle samples were tested and compared between the two groups.Results:The serum IL-1β and IL-18 levels were significantly higher in DM/PM patients than those in the controls by enzyme linked immunosorbent assay (ELISA,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-1 β,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-1β and IL-18 and could be one of the factors promoting disease progress.