HMGB1在类风湿关节炎疾病活动中的作用及其与EMMPRIN/CD147表达的相关性研究

目的:探讨高迁移率族蛋白(HMGB)1在类风湿关节炎(RA)病情活动中的作用机制.方法:选取RA患者74例(活动期38例、非活动期36例)及健康对照者26例.采用RT-PCR方法检测外周血单个核细胞(PBMC)中HMGB1 mRNA的表达,酶联免疫吸附(ELISA)方法检测血清中HMGB1蛋白的表达.采用流式细胞术分析CD14+单核细胞表面Toll样受体(TLR)4和EMMPRIN/CD147的表达.结果:活动期RA组HMGB1 mRNA相对表达量和蛋白水平均高于健康对照者和非活动期RA患者[分别为2.63 vs 0.71,0.93和 (10.20±1.24 vs 7.48±1.75,8.31±1.85)ng/ml)](P＜0.01).活动期RA患者CD14+单核细胞上TLR4和CD147的表达量均显著高于非活动期和健康对照组(P＜0.01),非活动期患者显著高于健康对照组(P＜0.01).TLR4和CD147双阳性细胞数量和蛋白的相对表达量在活动期RA患者中均最高.血清中HMGB1蛋白水平与ESR、CRP、RF、及关节X线分期均呈正相关,亦与TLR4和CD147的表达呈正相关(P＜0.05或P＜0.01).结论:RA患者PBMC具有合成和分泌HMGB1蛋白的功能.HMGB1可能通过与TLR4结合激活CD14+单核细胞并表达CD147,促进其向滑膜组织迁移而加速骨质破坏.     

TLR4介导高迁移率族蛋白致系统性红斑狼疮肾损害的作用研究

目的 探讨高迁移率族蛋白1(HMGB1)致红斑性狼疮肾损害的作用机制与Toll样受体4(Toll-like receptor 4,TLR4)表达的相关性.方法 ELISA检测12例健康对照组、16例系统性红斑狼疮(systemic lupus eqrthematosus,SLE)无肾脏损害和18例狼疮性肾炎(lupus nephritis,LN)患者血清中HMGB1、基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶组织抑制剂-2(TIMP-2)的表达情况;流式细胞术检测外周血CD3/TLR4和CD14/TLR4表达情况;分离外周血单个核细胞(PBMC),RT-PCR检测HMGB1 mRNA的表达变化.结果 HMGB1 mRNA相对表达量及血清中HMGB1蛋白在LN组明显高于SLE组和健康对照组;流式细胞术显示CD14+的单核细胞表面HMGB1受体TLR4在LN组表达最高(P＜0.05),且与尿蛋白呈正相关(P＜0.01);LN患者血清中MMP-2和TIMP-2蛋白的浓度明显低于SLE和健康对照组,同时MMP-2/TIMP-2比值下降.HMGB1 mRNA及CD14+/TLR4+与MMP-2/TIMP-2比值均呈显著负相关;LN组患者血清中HMGB1蛋白水平与蛋白尿呈正相关,与MMP-2/TIMP-2比值呈显著负相关.结论 HMGB1是狼疮性肾炎发病中的重要细胞因子;HMGB1可能部分通过TLR4激活PBMC,降低MMP-2/TIMP-2的活性,从而引起蛋白尿.     

ICOS/ICOSL在类风湿关节炎患者外周血淋巴细胞的表达及临床意义

目的:检测初发类风湿关节炎(Rheumatoid arthritis,RA)患者外周血淋巴细胞表面共刺激分子ICOS和ICOSL的表达,并探讨其临床意义。方法:采用流式细胞术和RT-PCR的方法,检测85例初发RA患者和50例健康对照(Healthy control,HC)外周血CD4+T细胞表面ICOS及CD14+单核细胞和CD19+B细胞表面ICOSL的表达,比较15例初诊RA患者治疗前后ICOS和ICOSL表达水平变化,分析其临床意义。结果:RA患者外周血中ICOS/ICOSL的mRNA的表达水平显著高于HC。RA患者外周血CD4+T细胞表面ICOS表达显著增高[(7.08±4.72)%vs(3.01±1.39)%,P0.0001]。RA患者外周血中CD14+单核细胞[(5.77±3.45)%vs(3.64±1.43)%,P0.05]和CD19+B细胞[(5.78±4.52)%vs(3.97±1.63)%,P0.05]表面ICOSL的表达均高于HC。活动期的RA患者外周血单核细胞和B细胞表面的ICOSL表达高于非活动期患者[(5.45±3.50)%vs(4.04±1.55)%,P=0.036]、[(6.59±5.74)%vs(5.63±4.30)%,P=0.016],治疗后CD4+T细胞表面ICOS的表达及CD14+单核细胞和CD19+B细胞表面ICOSL的表达均显著下降[(3.33±0.31)%vs(5.56±1.11)%,P=0.076]、[(5.12±1.23)%vs(9.99±2.02)%,P=0.045]、[(3.74±0.57)%vs(8.62±1.77)%,P=0.011]。结论:RA患者外周血单个核细胞表面ICOS和ICOSL异常高表达,且与疾病活动度和临床疗效密切相关。提示ICOS/ICOSL信号通路可能参与RA免疫病理进程。     

RA患者外周血CD4~+CD25~+Foxp3~+Treg细胞比例及中性粒细胞表面CD200R1的分析

本研究探讨类风湿关节炎(rheumatoid arthritis,RA)患者外周血CD4~+CD25~+Foxp3~+Treg细胞的百分含量和中性粒细胞表面CD200R1的表达情况,并探讨其临床意义。采用流式细胞术分别检测RA患者和健康对照组外周血CD4~+CD25~+Foxp3~+Treg细胞的百分含量和中性粒细胞表面CD200R1的阳性表达率。ELISA检测其血清中单核细胞趋化蛋白-1(monocyte chemotactic protein-1,MCP-1)和CCR2的表达水平。实验结果显示:RA患者外周血CD4~+CD25~+Foxp3~+Treg细胞占CD4~+T细胞的比例明显低于健康对照组,中性粒细胞表面CD200R1的阳性表达率明显高于健康对照组,RA患者血清中MCP-1与CCR2的表达水平明显高于健康对照组。以上结果提示CD200/CD200R1信号异常,CD4~+CD25~+Foxp3~+Treg细胞数量减少可能为RA的发病机制之一,调控CD200/CD200R1信号和CCR2~+Treg细胞输注可能成为RA治疗的新靶点。     

类风湿关节炎患者外周血单个核细胞Notch及其配体表达

为研究Notch信号途径在类风湿关节炎(RA)发病机制中的作用,选取活动期RA患者,采用流式细胞术结合细胞表面及细胞内染色技术检测外周血单个核细胞Notch受体及配体表达情况,并与正常对照进行比较。结果发现,活动期RA患者外周血T细胞Notch2、Notch3及Notch4表达较正常人明显增加,Notch1分子表达均较少,二者未见差异。其中表达Notch分子的细胞以CD4+T细胞为主。二者B细胞Notch1、Notch2、Notch3及Notch4的表达均较低,之间未见明显差异。RA患者单核细胞Jagged1分子表达明显增加,而Delta1表达降低。结果提示活动期RA患者外周血单个核细胞中不同群体细胞存在Notch及其配体表达水平的改变。     

高迁移率族蛋白及其TOLL 样受体4在系统性红斑狼疮肾脏损害中的作用

目的：探讨高迁移率族蛋白1（HMGB1）及其受体TOLL样受体（TLR）-4在系统性红斑狼疮肾脏损害中的作用。方法：ELISA检测12例健康对照组、16例系统性红斑狼疮无肾脏损害（Systemic lupus erythematosus,SLE）和18例合并肾脏损害的系统性红斑狼疮患者（Lupus nephritis,LN）血清中HMGB1表达情况;流式细胞术检测外周血CD3/TLR-4和CD14/TLR-4表达情况;分离外周血单个核细胞,RT-PCR检测HMGB1mRNA的表达变化。结果：血清中HMGB1蛋白在LN组明显高于SLE组和健康对照组,而SLE组和健康对照组之间差异无统计学意义;LN组患者HMGB1mRNA相对表达量均高于对照组和SLE组患者;流式细胞术显示CD14＋的单核细胞表面HMGB1受体TLR4在LN组表达最高（P〈0.05）,且与尿蛋白呈正相关（P〈0.01）,而CD3＋的淋巴细胞表面HMGB1受体TLR4表达率在各组间无显著性差异（P〉0.05）。结论：狼疮性肾炎患者PBMC能主动合成、分泌HMGB1,使患者血清中表达水平明显升高;HMGB1可能部分通过TLR4激活PBMC,介导炎症反应,从而引起肾脏损害。     

HMGB1及TLR2在多发性硬化患者外周血单核细胞中的表达及其作用

通过检测高迁移率族蛋白B1(high mobility group protein B1,HMGB1)及Toll样受体2(toll like receptor 2,TLR2)在多发性硬化(multiple sclerosis,MS)患者外周血单个核细胞(peripheral blood mononuclear cell,PBMC)中的表达变化及血清中单核细胞趋化蛋白1(monocyte chemotactic protein 1,MCP-1)、IL-17分泌变化,初步探讨HMGB1及TLR2在MS发病中可能的免疫学作用。应用流式细胞术检测MS患者组、健康对照组人群PBMC中HMGB1及TLR2蛋白的相对表达并采用Pearson相关分析观察两者表达的相关性;应用ELISA法检测两组人群血清中MCP-1、IL-17分泌水平。MS组HMGB1、TLR2蛋白的相对表达及MCP-1、IL-17分泌水平较对照组明显上调(P0.01),HMGB1蛋白与TLR2蛋白表达呈正相关(r=0.893,P0.01)。HMGB1可能会通过其受体TLR2启动下游炎性信号传导通路,参与MS免疫损伤过程。     

可溶性和膜型B7-H3在类风湿关节炎患者外周血中的表达及临床意义

本实验通过检测类风湿关节炎(RA)患者外周血中可溶性B7-H3(sB7-H3)和膜型B7-H3(mB7-H3)的表达及异构体的分布,探讨该分子的异常表达在RA发病中的临床意义。通过收集RA早期患者和健康对照外周血,ELISA方法检测血清中sB7-H3的表达,统计学分析sB7-H3的表达与临床的相关性;同时分离RA患者和健康对照外周血单个核细胞(periph-eral blood mononuclear cells,PBMC),通过流式细胞术检测CD14+的单核细胞膜型B7-H3的变化;通过PCR检测外周血mRNA水平B7-H3两种异构体的表达。结果显示RA患者血清中的sB7-H3分子明显低于健康对照组,RA活动期患者sB7-H3明显低于缓解期患者,并与RA患者肿胀关节数呈负相关;RA患者外周血单核细胞上mB7-H3的表达明显高于健康对照者,RA患者PBMC在mRNA水平B7-H3明显高于健康对照者,主要表达形式为4IgB7-H3。本研究发现膜型和可溶性B7-H3在类风湿性关节炎外周血中异常表达,其可能参与了RA自身免疫性病理的调节。     

Notch1与TLR2相互作用调控CD14~+单核细胞功能在冠状动脉粥样硬化性心脏病中的作用

目的观察Notch1/2分子和Toll样受体(TLR)在冠心病患者中的表达变化,探讨Notch信号通路与TLR2的相互作用对CD14~+单核细胞的调控作用。方法本研究入组稳定性心绞痛(SA)22例、不稳定性心绞痛(UA)34例、急性心肌梗死(AMI)27例,同时入组31例健康对照者。实时定量PCR法检测PBMC中Notch1/2以及TLR1-10 mRNA的相对表达量。分选CD14~+单核细胞,应用Notch信号通路抑制剂DAPT和/或TLR2激动剂Pam3Csk4刺激培养24 h,检测TLR2和Notch信号通路相关分子的表达变化,ELISA法检测上清中促炎细胞因子的表达变化,Western blot法检测细胞中抗髓样分化因子88(MyD88)和TIR结构域接头分子(TRIF)的水平。结果 Notch1 mRNA的相对表达量在AMI组显著升高,Notch2 m RNA的相对表达量在各组间的差异无统计学意义。TLR4、TLR7、TLR9 mRNA的相对表达量在SA组、UA组和AMI组中均显著高于NC组,TLR2 mRNA的相对表达量在AMI组中显著高于NC组、SA组和UA组。DAPT刺激可降低CD14~+单核细胞中TLR2 m RNA的相对表达量,对TLR4、TLR7和TLR9 mRNA的表达无显著影响。Pam3Csk4刺激可升高AMI患者CD14~+单核细胞中Notch1 mRNA的相对表达量,Notch信号通路相关分子Hes1和Hes5 mRNA的相对表达量亦显著升高。DAPT刺激还可抑制AMI患者中TLR2介导的炎症信号通路的应答,降低Pam3Csk4刺激后AMI患者CD14~+单核细胞培养上清中白细胞介素(IL)-6、IL-8和肿瘤坏死因子-α的表达,这一过程主要通过影响TIR结构域接头分子表达及核因子-κB的磷酸化而实现。结论 Notch1和TLR2的相互作用可能发挥调控冠心病患者CD14~+单核细胞功能的作用。     

类风湿性关节炎活动期外周血CT4+T细胞的表型变化

目的观察类风湿性关节炎(RA)活动期外周血CT4+T淋巴细胞的表型变化,探讨其免疫病理机制。方法采用ELISA和双标记免疫荧光法检测50例活动期RA患者和50例健康成人外周血CD4+T细胞表面CD154、CD69的表达以及血清、血浆可溶性CD154(sCD154)的含量。结果活动期RA患者的外周血CD4+T细胞CD154(16.8%±7.9%)和CD69(14.1%±8.2%)的表达水平均显著高于健康人,其血清sCD154(18.56±6.32,ng/ml)和血浆sCD154(8.41±3.51,ng/ml)含量亦分别高于健康人血清sCD154(9.56±4.71,ng/ml)和血浆sCD154(2.98±1.13,ng/ml)。结论CD4+T细胞表达的CD154、CD69以及血浆sCD154含量与RA的活动相关,可以作为RA的辅助诊断、疗效评价和预后判断的有价值的实验室参数。     

HMGB1 Promotes the Differentiation of Th17 via Up‐Regulating TLR2 and IL‐23 of CD14+ Monocytes from Patients with Rheumatoid Arthritis

High‐mobility group box 1 (HMGB1) is a non‐histone nuclear protein that is released extracellulary and has been implicated in autoimmune disease. Toll‐like receptor 2 (TLR2) signalling is thought to be essential for the inflammatory response and for immune disorders. In recent studies, enhanced HMGB1 and TLR2 expressions have been found in rheumatoid arthritis (RA), respectively. The aim of this study is to explore whether HMGB1 stimulation can up‐regulate the expression of TLR2 on CD14⁺ monocytes from patients with RA and to clarify the subsequent events involving Th17 cells and Th17 cell‐associated cytokine changes. Our results showed that the frequency of CD14⁺ cells in peripheral blood mononuclear cell (PBMC) was obviously increased, and enhanced expression of TLR2 on CD14⁺ monocytes was also found in patients with RA, compared with healthy controls with statistical significance (P < 0.001). In addition, the levels of IL‐17, IL‐23 and IL‐6 in supernatants from cultured monocytes from patients and in patient’s plasma were increased, and NF‐κB, the downstream target of TLR2, also showed a marked elevation after monocytes were stimulated by HMGB1. This implies that the enhanced TLR2 pathway and Th17 cell polarization may be due to HMGB1 stimulation in rheumatoid arthritis.     

The damage‐associated molecular pattern HMGB1 is elevated in human alcoholic hepatitis,but does not seem to be a primary driver of inflammation

The role of sterile inflammation caused by release of damage‐associated molecular patterns (DAMP) remains unclear in human alcoholic hepatitis (AH). The DAMP, high mobility group box‐1 protein (HMGB1) is released by tissue damage and inflammation. We aimed to investigate whether HMGB1 is a primary inflammatory driver in AH by determining HMGB1 serum levels and effects on inflammatory cells from AH patients. We measured serum HMGB1 in 34 AH patients and 10 healthy controls using ELISA. Toll‐like receptor 4 (TLR4) and CD14 expressions were assessed by flow cytometry on HMGB1‐stimulated peripheral blood mononuclear cells (PBMC) and ELISA was used to measure TNF‐α and IL‐1β in the supernatants. We observed 5‐fold higher serum levels of HMGB1 in AH patients at the day of diagnosis and day 30, but no associations to clinical outcome. HMGB1 stimulation increased the expression of TLR4 on CD14+‐monocytes compared with unstimulated cells in the AH patients. The TNF‐α and IL‐1β production in response to HMGB1 was diminished in AH patients. In conclusion, AH patients have increased levels of HMGB1 in their blood. This combined with an increased TLR4 expression, but an unaffected cytokine response to HMGB1 suggest that HMGB1 is not the primary driver of inflammation in AH.     

T-cell functional defects in rheumatoid arthritis: intrinsic or extrinsic?

This study investigated two mechanisms which may underlie abnormal T-cell function [lymphocyte proliferation and interleukin-2 (IL-2) production] in rheumatoid arthritis (RA). These were: (a) a possible lack of the IL-2-producing CD4+2H4+ lymphocytes and (b) the possible inhibitory role of monocytes and neutrophils. Numbers of CD4+2H4+ cells did not differ between normal controls and patients with RA, although IL-2 produced by the peripheral blood mononuclear cells (PBMC) of the same individuals was markedly reduced in the patient group (P less than 0.001). Many rheumatoid peripheral blood mononuclear cell preparations, but very few control, were contaminated with neutrophils (P less than 0.001). This was more marked in patients with active RA than in those with inactive disease (P less than 0.001). Numbers of monocytes were similar in all groups. Monocyte depletion, or addition of indomethacin and/or catalase in PBMC, caused a significantly greater increase of responses in RA patients than in controls. This effect was significantly higher in patients with active disease than in the inactive group. These findings suggest that activated monocytes and neutrophils found in the rheumatoid PBMC preparations exert inhibitory effects mediated, in part, by the production of prostaglandins and reactive oxygen intermediates. Monocyte depletion and partial reconstitution resulted in significant increase of lymphocyte proliferation and IL-2 production in both controls and patients. None of the manipulations performed succeeded in normalizing the deficient rheumatoid T-cell responses. These data support the hypothesis that non-lymphoid cell populations play an important role in the T-cell dysfunction characteristic of RA.(ABSTRACT TRUNCATED AT 250 WORDS)     

类风湿关节炎患者外周血单核细胞亚群的变化及其意义

目的:本次研究通过检测类风湿关节炎(RA)患者外周血单核细胞亚群比例及其分泌促炎细胞因子的功能,探讨单核细胞亚群在RA 发病过程中的作用。方法:22 例RA 患者(RA 组)和22 例健康对照者(HC 组),经知情同意后抽取3ml 静脉血,肝素钠抗凝。流式细胞术(FCM)检测单核细胞亚群比例、中间型单核细胞表面HLA-DR、Toll 样受体2(TLR2)和髓系细胞触发受体-1(TREM-1)表达,及其细胞内肿瘤坏死因子(TNF)鄄琢平均荧光强度(MFI),并分析RA 患者单核细胞亚群比例与血清细胞因子的相关性。正态数据分析采用Students’t-test 检验。结果:与HC 组相比,RA 组中间型单核细胞比例升高[(4.6±1.2)% vs (11.7±1.6)%],差异有统计学意义(P<0.05);HLA-DR 表达(MFI)与HC 组比较差异无统计学意义(26.8±8.6 vs 30.2±6.1,P>0.05)。RA 组TLR2(750.2±110.3 vs 526.8±98.6)、TREM-1(58.4±12.1 vs 40.3依10.2)表达(MFI)高于HC 组,差异均有统计学意义(P<0.05);RA 组中间型单核细胞胞内TNF鄄琢(46.3±6.4 vs 36.7±8.3)MFI 高于HC 组,差异有统计学意义(P<0.05)。RA 患者中间型单核细胞比例与DAS28 评分和血清TNF 、白细胞介素(IL)-17 呈正相关,相关系数分别为0.593(P =0.003)、0.471(P =0.027) 和0.538(P =0.009)。结论:RA 患者外周血单核细胞向中间型极化,并处于活化状态,高表达TLR2 和TREM-1,分泌较多的促炎细胞因子TNF ,参与RA 的疾病过程。因此,抑制单核细胞向中间型极化或阻断表面受体表达可能是治疗RA 的新途径。     

The impact of acute strenuous exercise on TLR2, TLR4 and HLA.DR expression on human blood monocytes induced by autologous serum

Acute exercise alters the surface expression of toll-like receptors (TLRs) and HLA.DR on blood monocytes, which could transiently compromise immunity. As serum factors might be responsible, we examined the effects of autologous post-exercise serum exposure on TLR2, TLR4 and HLA.DR expression on resting blood monocytes and their subtypes. Eight trained cyclists completed an ergometer 60 km time trial. PBMCs and serum were obtained before, immediately after and 1 h after exercise. TLR2, TLR4 or HLA.DR expression (gMFI) was determined on blood monocyte subtypes expressing combinations of CD14 and CD16 by flow cytometry, and on resting monocytes exposed to 50% autologous serum (pre, immediately after or 1 h after exercise) for 18 h in culture. Immediately after exercise, total monocyte expression of TLR2 and TLR4 increased by 41 and 27%, respectively, while HLA.DR expression was 39% lower than baseline. TLR2 and TLR4 was 53 and 84% greater 1 h after exercise, respectively, while HLA.DR was 48% lower. Changes in TLR2 and TLR4 expression occurred on the CD14^++bright/CD16^+dim monocyte subtype only, while HLA.DR expression changed on the CD14^+dim/CD16^++bright subtype. Serum did not affect monocyte TLR2 or TLR4 expression but 1 h post serum increased expression of HLA.DR on total monocytes and the CD14^+dim/CD16^++bright subtype, which was in contrast to the change observed at this time after exercise. We conclude that a bout of strenuous aerobic exercise alters the surface expression of TLR2, TLR4 and HLA.DR on blood monocytes and some of their subtypes, but these changes appear to be unrelated to blood serum factors.     

IL-38 抑制LPS / TLR4 诱导炎症减轻类风湿关节炎的机制研究

目的:探讨IL-38 和TLR4 在类风湿关节炎中的潜在关联及其在类风湿性关节炎中致病的机制。方法:选取2013 年1 月至2016 年2 月间本院收治的41 例类风湿关节炎患者(观察组)及45 例本院实施创伤后滑膜切除术的患者(对照组)为研究对象。收集观察组和对照组的外周血单个核细胞(PBMCs)、滑膜组织及血清。荧光定量PCR 检测PBMCs 及滑膜组织中IL-38 及TLR4 的mRNA 水平。ELISA 检测滑膜液及血清中IL-38 的表达,Western blot 检测滑膜组织中IL-38 及TLR4的表达。LPS 和/ 或IL-38 刺激RAW264.7 细胞,ELISA 检测RAW264.7 细胞上清中IL-6、IL-8 及TNF-α的含量,荧光定量PCR检测RAW264.7 细胞TLR4、IL-6、IL-8 及TNF-α的表达。NF-κB 激活-核转运试剂盒及Western blot 检测NF-κB 信号的激活水平。结果:与对照组相比,类风湿关节炎患者PBMCs、血清及滑膜组织和滑膜液中IL-38 水平显著升高,而TLR4 水平也显著升高,Pearson 相关分析显示二者呈负相关。LPS 和/ 或IL-38 刺激RAW264.7 细胞后,IL-38 能够抑制LPS 诱导的TLR4、IL-6、IL-8 及TNF-α表达,进一步的分析显示,IL-38 能抑制NF-κB 信号途径激活,因此推测IL-38 可能是通过抑制NF-κB 信号途径激活从而抑制LPS/ TLR4 信号诱导的炎症因子表达。结论:IL-38 能抑制LPS/ TLR4 诱导炎症减轻类风湿关节炎,其机制可能是通过抑制NF-κB 信号途径的激活。     

Expression and activity of AIM2-inflammasome in rheumatoid arthritis patients

IntroductionAIM2 inflammasome activation leads to the release of IL-β, which plays an important role in rheumatoid arthritis pathogenesis. In this work, we evaluated AIM2 expression and activity in RA patients and healthy controls.MethodsAIM2 and RANKL expression were evaluated by flow cytometry. Inflammasome activity was determined in monocyte cultures stimulated with synthetic DNA by measuring IL-1β levels in supernatants using an ELISA assay. The caspase-1 expression in monocytes was measured by western blot, the POP3 expression was analysed by qPCR, and serum levels of IFN-γ were evaluated using ELISA assay. Results: We observed a diminution of CD14+AIM2+ cells in RA patients, associated with disease activity and evolution. Likewise, the levels of IL-1β were increased in monocyte cultures un-stimulated and stimulated with LPS from RA patients with DAS28 ≥ 4. The Caspase-1 activity and RANKL + monocytes in RA patients were slightly increased. Finally, augmented POP3 expression and diminished IFN-γ serum levels were detected in RA patients.ConclusionOur results showed that the monocytes from RA patients were prone to release IL-1β in the absence of the AIM2 inflammasome signal. The down-regulation of AIM2 to a systemic level in RA patients might be a consequence of augmented POP3 expression and might imply the survival of pro-inflammatory cells contributing to the inflammation process.     

Exercise training-induced lowering of inflammatory (CD14+CD16+) monocytes: a role in the anti-inflammatory influence of exercise?

Exercise training or higher levels of physical activity are known to exert anti-inflammatory effects. CD14+CD16+ monocytes are potent producers of inflammatory proteins, and elevated levels of these "inflammatory" monocytes have been implicated in disease development. Little is known about the influence of exercise training on this cell population. On the basis of their physical activity pattern, male and female subjects, 65-80 years old, were assigned to a physically active (PA; n=15) or inactive (PI; n=15) group. The PI group performed 12 weeks (3 days/week) of endurance (20 min at 70-80% heart-rate reserve) and resistance exercise training (eight exercises, two sets at 70-80% of one repetition maximum). Subjects in the PA group maintained their habitual activity level. Flow cytometry was used to determine monocyte phenotype and monocyte TLR4 expression. ELISAs were used to measure whole blood, LPS-stimulated TNF-alpha production, and serum C-reactive protein (CRP). At baseline, the PA group had a lower percentage of CD14+CD16+ monocytes and lower unstimulated production of TNF-alpha than the PI group. CD14+CD16+ monocyte percentage and 1 ng/ml LPS-stimulated TNF-alpha production were reduced after the PI group underwent 12 weeks of exercise training. PI subjects also had higher TLR4 expression on classical monocytes, but there were no significant exercise training-induced changes in monocyte TLR4 expression. The PA group had significantly lower serum CRP than the PI group. Physical activity was associated with lower CD14+CD16+ monocyte percentage and LPS-stimulated TNF-alpha production. Exercise training-induced reductions in CD14+CD16+ monocytes may contribute to the anti-inflammatory effects of exercise training.