Involvement of TLR7 MyD88-dependent signaling pathway in the pathogenesis of adult-onset Still's disease.
Involvement of TLR7 MyD88-dependent signaling pathway in the pathogenesis of adult-onset Still's disease.
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TLR7 MyD88依赖性信号通路参与成人发病的发病机理。
DOI：
10.1186/ar4193
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发表时间：
2013-03-04
影响因子：
4.9
通讯作者：
Hsieh CW
中科院分区：
文献类型：
--
作者：
Chen DY;Lin CC;Chen YM;Lan JL;Hung WT;Chen HH;Lai KL;Hsieh CW
本研究的目的是探讨toll样受体7 （TLR7）信号通路在成人发病斯蒂尔氏病（AOSD）发病机制中的潜在作用。采用流式细胞术分析28例AOSD患者、28例系统性红斑狼疮患者和12例健康对照（HC）中髓样树突状细胞（mDCs）和mDCs前体细胞tlr7表达频率。采用定量PCR和western blotting分别检测外周血单核细胞TLR7信号分子转录和蛋白水平。ELISA法检测血清细胞因子水平。AOSD患者（分别为65.5%和14.9%）和SLE患者（分别为60.3%和14.4%）表达tlr7的pre-mDCs和mDCs的中位数频率显著高于HC患者（分别为42.8%和8.8%，P均<0.001）。与HC患者相比，AOSD患者和SLE患者的tlr7信号分子转录和蛋白水平上调，包括MyD88、TRAF6、IRAK4和IFN-α。在AOSD和SLE患者中，疾病活动度评分与TLR7表达mDCs的频率和TLR7信号分子的表达水平呈正相关。TLR7配体（咪喹莫特）刺激PBMCs可显著提高AOSD和SLE患者的白细胞介素(IL)-1β、IL-6、IL-18和IFN-α水平。经有效治疗后，表达TLR7的mDCs的频率和TLR7信号分子的表达水平显著降低。在AOSD患者中，TLR7信号分子水平的升高及其与疾病活动的正相关表明TLR7信号通路参与了该疾病的发病机制。TLR7 myd88依赖性信号分子的过表达可能是AOSD和SLE的共同致病机制。
The objective of this study was to investigate the potential role of the Toll-like receptor 7 (TLR7) signaling pathway in the pathogenesis of adult-onset Still's disease (AOSD). Frequencies of TLR7-expressing precursor of myeloid dendritic cells (pre-mDCs) and mDCs in 28 AOSD patients, 28 patients with systemic lupus erythematosus (SLE) and 12 healthy controls (HC) were determined by flow cytometry analysis. Transcript and protein levels of TLR7 signaling molecules in peripheral blood mononuclear cells (PBMCs) were evaluated by quantitative PCR and western blotting respectively. Serum cytokines levels were measured by ELISA. Significantly higher median frequencies of TLR7-expressing pre-mDCs and mDCs were observed in AOSD patients (65.5% and 14.9%, respectively) and in SLE patients (60.3% and 14.4%, respectively) than in HC (42.8% and 8.8%, respectively; both P <0.001). Transcript and protein levels of TLR7-signaling molecules, including MyD88, TRAF6, IRAK4 and IFN-α, were upregulated in AOSD patients and SLE patients compared with those in HC. Disease activity scores were positively correlated with the frequencies of TLR7-expressing mDCs and expression levels of TLR7 signaling molecules in both AOSD and SLE patients. TLR7 ligand (imiquimod) stimulation of PBMCs resulted in significantly enhanced levels of interleukin (IL)-1β, IL-6, IL-18 and IFN-α in AOSD and SLE patients. Frequencies of TLR7-expressing mDCs and expression levels of TLR7 signaling molecules significantly decreased after effective therapy. Elevated levels of TLR7 signaling molecules and their positive correlation with disease activity in AOSD patients suggest involvement of the TLR7 signaling pathway in the pathogenesis of this disease. The overexpression of TLR7 MyD88-dependent signaling molecules may be a common pathogenic mechanism for both AOSD and SLE.
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影响因子：
4.9
作者：
Kawasaki A;Furukawa H;Kondo Y;Ito S;Hayashi T;Kusaoi M;Matsumoto I;Tohma S;Takasaki Y;Hashimoto H;Sumida T;Tsuchiya N
通讯作者：
Tsuchiya N
影响因子：
4.4
作者：
Hamilton-Williams, EE;Lang, A;Kurts, C
通讯作者：
Kurts, C
DOI：
10.1084/jem.20101048
发表时间：
2010-12-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Guiducci C;Tripodo C;Gong M;Sangaletti S;Colombo MP;Coffman RL;Barrat FJ
通讯作者：
Barrat FJ
影响因子：
5.5
作者：
Chen, Der-Yuan;Chen, Yi-Ming;Hsieh, Chia-Wei
通讯作者：
Hsieh, Chia-Wei
影响因子：
64.8
作者：
Hemmi, H;Takeuchi, O;Akira, S
通讯作者：
Akira, S