促炎细胞因子白细胞介素1β(IL-1β)和白细胞介素18(IL-18)主要由巨噬细胞和树突细胞产生,是宿主针对各种侵入病原体产生先天免疫应答的重要介质。这些促炎细胞因子从病毒感染的细胞中分泌,被称为炎症小体的多蛋白复合物严格调控。根据...促炎细胞因子白细胞介素1β(IL-1β)和白细胞介素18(IL-18)主要由巨噬细胞和树突细胞产生,是宿主针对各种侵入病原体产生先天免疫应答的重要介质。这些促炎细胞因子从病毒感染的细胞中分泌,被称为炎症小体的多蛋白复合物严格调控。根据炎症小体识别蛋白的种类,炎症小体主要分为两类,即核苷酸结合寡聚结构域样受体(NOD-like receptors,NLRs)和黑色素瘤缺乏因子2样受体(Absent in melanoma 2,AIM2)炎症小体。与其他宿主防御机制不同,炎症小体活化后,会诱导促炎细胞因子IL-1β、IL-18的成熟及分泌。适量的促炎细胞因子有利于控制病理性感染,但如果过量,则会对机体造成一定免疫损伤。本文主要对近几年有关病毒感染对炎症小体的激活和抑制机制进行了综述,总结分析了炎症小体在参与天然免疫反应及病毒感染致病过程中具有的重要作用。展开更多
NOD样受体家族含pyrin结构域蛋白3(NOD-like receptor family pyrin domain-containing protein 3,NLRP3)炎症小体是一种蛋白质复合体,可促进Caspase的活化和IL-1β的成熟,在多种炎症的发生、发展过程中起促进作用。牙周炎(periodontiti...NOD样受体家族含pyrin结构域蛋白3(NOD-like receptor family pyrin domain-containing protein 3,NLRP3)炎症小体是一种蛋白质复合体,可促进Caspase的活化和IL-1β的成熟,在多种炎症的发生、发展过程中起促进作用。牙周炎(periodontitis,PD)的发生与牙周组织的菌群失调有关,NLRP3炎症小体参与中性粒细胞、巨噬细胞、破骨细胞(osteoclast,OC)和人牙周膜成纤维细胞(human periodontal liqament fibroblast,HPLF)的活化过程。该文归纳了相关免疫细胞及基质细胞的NLRP3炎症小体对PD的影响,并简述了与NLRP3炎症小体相关的PD治疗新思路。展开更多
Background： Cryopyrin-associated periodic syndrome （CAPS） is a group of rare, heterogeneous autoinflammatory disease characterized by interleukin （IL）-1β-mediated systemic inflammation and clinical symptoms invo...Background： Cryopyrin-associated periodic syndrome （CAPS） is a group of rare, heterogeneous autoinflammatory disease characterized by interleukin （IL）-1β-mediated systemic inflammation and clinical symptoms involving skin, joints, central nervous system, and eyes. It encompasses a spectrum of three clinically overlapping autoinflammatory syndromes including familial cold autoinflammatory syndrome, Muckle-Wells syndrome （MWS）, and neonatal-onset multisystem inflammatory disease. CAPS is associated with gain-of-function missense mutations in NOD-like receptor family pyrin domain-containing protein 3 （NLRP3）, the gene encoding NLRP3. Moreover, most mutations leading to MWS occurred in exon 3 ofNLRP3 gene. Here, we reported a novel mutation occurred in exon 1 ofNLRP3 gene in an MWS patient and attempted to explore the pathogenic mechanism. Methods： Genetic sequence analysis of NLRP3 was performed in an MWS patient who presented with periodic lever, arthralgia, and multiform skin lesions. NLRP3 was also analyzed in this patient＇s parents and 50 healthy individuals. Clinical examinations including X-ray examination, skin biopsy, bone marrow aspiration smear, and blood test of C-reactive protein （CRP）, erythrocyte sedimentation rate （ESR）, serum levels oflL-1β, immunoglobulin E （lgE）, antineutrophil cytoplasmic antibodies, antinuclear antibodies, and extractable nuclear antigen were also analyzed. The protein structure of mutant NLRP3 inflammasome was calculated by SWISS-MODEL software. Proteins of wild type and mutant components ofNLRP3 inflammasome were expressed and purified, and the interaction abilities between these proteins were tested by surface plasmon resonance （SPR） assay. Results： X-ray examination showed no abnormality in the patient＇s knees. Laboratory tests indicated an elevation of CRP （233.24 nag/L） and ESR （67 mm/h） when the patient had fever. Serum IL-1β increased to 24.37 pg/ml, and serum lgE was higher than 2500.00 IU/ml. Other blood tests were no展开更多
慢性肾脏病发病率逐年上升,现已成为威胁全世界公共健康的主要疾病之一。导致慢性肾脏病的基本病因众多,主要包括原发性与继发性肾小球肾炎、糖尿病肾脏疾病、高血压肾损害、肾小管间质病变、遗传性疾病等。而糖尿病肾脏疾病作为慢性肾...慢性肾脏病发病率逐年上升,现已成为威胁全世界公共健康的主要疾病之一。导致慢性肾脏病的基本病因众多,主要包括原发性与继发性肾小球肾炎、糖尿病肾脏疾病、高血压肾损害、肾小管间质病变、遗传性疾病等。而糖尿病肾脏疾病作为慢性肾脏病的病因之一,是糖尿病引起的肾脏微血管病变的并发症,不加以控制可进展为终末期肾病。糖尿病肾脏疾病的具体发病机制尚不完全清晰,主要以高糖等代谢因素导致的免疫介导性炎症对肾脏破坏为主,而近年来发现免疫介导性炎症因素是糖尿病肾脏疾病发生的重要原因之一。在糖尿病肾脏疾病中,机体处在高糖状态下募集如白介素、肿瘤坏死因子等炎症反应细胞在肾脏浸润,从而刺激肾脏微血管病变的发生,这一过程涉及多种信号通路的发生。在天然免疫应答系统中,Toll样受体4(toll like receptor 4,TLR4)以及Nod样受体蛋白3(nod-like receptor family pyrin domain-containing protein 3,NLRP3)炎性小体在肾脏相关免疫炎症疾病中扮演着重要角色。近来研究发现,TLR4以及NLRP3炎性小体与糖尿病肾脏疾病的发病机制密切相关。在高糖条件下可检测到TLR4水平的增高,而TLR4通过识别特异性配体激活核因子κB(nuclear factor-κB,NF-κB)从而激活下游炎症因子的成熟与释放,进一步促进肾脏病变。NLRP3炎性小体在糖尿病患者肾脏的足细胞、系膜细胞等少量存在,NF-κB的活化激活炎性小体的组装与成熟,从而促进炎症因子的释放。因此,TLR4、NLRP3在糖尿病肾脏疾病的发生、发展中发挥着重要作用,本文就这一研究展开相关的阐述。展开更多
为探究成人癫痫患者血清NOD样受体家族含pyrin结构域蛋白3(NOD-like receptor family pyrin domain-containing protein 3, NLRP3)水平对短期内(≤7 d)癫痫再发风险的预测价值,收集2018年9月—2019年8月于滨州医学院附属医院收治的61例...为探究成人癫痫患者血清NOD样受体家族含pyrin结构域蛋白3(NOD-like receptor family pyrin domain-containing protein 3, NLRP3)水平对短期内(≤7 d)癫痫再发风险的预测价值,收集2018年9月—2019年8月于滨州医学院附属医院收治的61例癫痫患者,其中丛集性发作者30例,非丛集性发作者31例。采集患者的一般资料,ELISA检测血清NLRP3炎症小体水平。根据住院后7 d内癫痫是否再发,分为癫痫再发组和未再发组,对一般资料进行统计学分析。随访过程中,有13例患者癫痫再次发作,比较2组发现,NLRP3水平、年龄、丛集性癫痫发生率有显著差异(均P<0.05)。多因素Logistic回归分析显示,NLRP3水平及年龄是癫痫患者短期内(≤7 d)再发的独立危险因素(均P<0.05)。NLRP3水平预测癫痫患者短期内再发的AUC为0.769(95%CI:0.608~0.931),截止值91.47μg/L,敏感度84.6%,特异度64.6%。以上结果表明,NLRP3水平对成人癫痫短期内再发有一定预测价值,阻断NLRP3生成可能有助于癫痫的治疗。展开更多
文摘促炎细胞因子白细胞介素1β(IL-1β)和白细胞介素18(IL-18)主要由巨噬细胞和树突细胞产生,是宿主针对各种侵入病原体产生先天免疫应答的重要介质。这些促炎细胞因子从病毒感染的细胞中分泌,被称为炎症小体的多蛋白复合物严格调控。根据炎症小体识别蛋白的种类,炎症小体主要分为两类,即核苷酸结合寡聚结构域样受体(NOD-like receptors,NLRs)和黑色素瘤缺乏因子2样受体(Absent in melanoma 2,AIM2)炎症小体。与其他宿主防御机制不同,炎症小体活化后,会诱导促炎细胞因子IL-1β、IL-18的成熟及分泌。适量的促炎细胞因子有利于控制病理性感染,但如果过量,则会对机体造成一定免疫损伤。本文主要对近几年有关病毒感染对炎症小体的激活和抑制机制进行了综述,总结分析了炎症小体在参与天然免疫反应及病毒感染致病过程中具有的重要作用。
文摘NOD样受体家族含pyrin结构域蛋白3(NOD-like receptor family pyrin domain-containing protein 3,NLRP3)炎症小体是一种蛋白质复合体,可促进Caspase的活化和IL-1β的成熟,在多种炎症的发生、发展过程中起促进作用。牙周炎(periodontitis,PD)的发生与牙周组织的菌群失调有关,NLRP3炎症小体参与中性粒细胞、巨噬细胞、破骨细胞(osteoclast,OC)和人牙周膜成纤维细胞(human periodontal liqament fibroblast,HPLF)的活化过程。该文归纳了相关免疫细胞及基质细胞的NLRP3炎症小体对PD的影响,并简述了与NLRP3炎症小体相关的PD治疗新思路。
基金This work was supported by the grant from the National Natural Science Foundation of China （No. 81201267）.
文摘Background： Cryopyrin-associated periodic syndrome （CAPS） is a group of rare, heterogeneous autoinflammatory disease characterized by interleukin （IL）-1β-mediated systemic inflammation and clinical symptoms involving skin, joints, central nervous system, and eyes. It encompasses a spectrum of three clinically overlapping autoinflammatory syndromes including familial cold autoinflammatory syndrome, Muckle-Wells syndrome （MWS）, and neonatal-onset multisystem inflammatory disease. CAPS is associated with gain-of-function missense mutations in NOD-like receptor family pyrin domain-containing protein 3 （NLRP3）, the gene encoding NLRP3. Moreover, most mutations leading to MWS occurred in exon 3 ofNLRP3 gene. Here, we reported a novel mutation occurred in exon 1 ofNLRP3 gene in an MWS patient and attempted to explore the pathogenic mechanism. Methods： Genetic sequence analysis of NLRP3 was performed in an MWS patient who presented with periodic lever, arthralgia, and multiform skin lesions. NLRP3 was also analyzed in this patient＇s parents and 50 healthy individuals. Clinical examinations including X-ray examination, skin biopsy, bone marrow aspiration smear, and blood test of C-reactive protein （CRP）, erythrocyte sedimentation rate （ESR）, serum levels oflL-1β, immunoglobulin E （lgE）, antineutrophil cytoplasmic antibodies, antinuclear antibodies, and extractable nuclear antigen were also analyzed. The protein structure of mutant NLRP3 inflammasome was calculated by SWISS-MODEL software. Proteins of wild type and mutant components ofNLRP3 inflammasome were expressed and purified, and the interaction abilities between these proteins were tested by surface plasmon resonance （SPR） assay. Results： X-ray examination showed no abnormality in the patient＇s knees. Laboratory tests indicated an elevation of CRP （233.24 nag/L） and ESR （67 mm/h） when the patient had fever. Serum IL-1β increased to 24.37 pg/ml, and serum lgE was higher than 2500.00 IU/ml. Other blood tests were no
文摘慢性肾脏病发病率逐年上升,现已成为威胁全世界公共健康的主要疾病之一。导致慢性肾脏病的基本病因众多,主要包括原发性与继发性肾小球肾炎、糖尿病肾脏疾病、高血压肾损害、肾小管间质病变、遗传性疾病等。而糖尿病肾脏疾病作为慢性肾脏病的病因之一,是糖尿病引起的肾脏微血管病变的并发症,不加以控制可进展为终末期肾病。糖尿病肾脏疾病的具体发病机制尚不完全清晰,主要以高糖等代谢因素导致的免疫介导性炎症对肾脏破坏为主,而近年来发现免疫介导性炎症因素是糖尿病肾脏疾病发生的重要原因之一。在糖尿病肾脏疾病中,机体处在高糖状态下募集如白介素、肿瘤坏死因子等炎症反应细胞在肾脏浸润,从而刺激肾脏微血管病变的发生,这一过程涉及多种信号通路的发生。在天然免疫应答系统中,Toll样受体4(toll like receptor 4,TLR4)以及Nod样受体蛋白3(nod-like receptor family pyrin domain-containing protein 3,NLRP3)炎性小体在肾脏相关免疫炎症疾病中扮演着重要角色。近来研究发现,TLR4以及NLRP3炎性小体与糖尿病肾脏疾病的发病机制密切相关。在高糖条件下可检测到TLR4水平的增高,而TLR4通过识别特异性配体激活核因子κB(nuclear factor-κB,NF-κB)从而激活下游炎症因子的成熟与释放,进一步促进肾脏病变。NLRP3炎性小体在糖尿病患者肾脏的足细胞、系膜细胞等少量存在,NF-κB的活化激活炎性小体的组装与成熟,从而促进炎症因子的释放。因此,TLR4、NLRP3在糖尿病肾脏疾病的发生、发展中发挥着重要作用,本文就这一研究展开相关的阐述。
