The role of interleukin-1 receptor-associated kinases in Vogt-Koyanagi-Harada disease.
The role of interleukin-1 receptor-associated kinases in Vogt-Koyanagi-Harada disease.
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Interleukin-1 受体相关激酶在 Vogt-Koyanagi-Harada 病中的作用
DOI：
10.1371/journal.pone.0093214
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ye J
中科院分区：
文献类型：
--
作者：
Sun M;Yang P;Du L;Yang Y;Ye J
目的探讨IRAK1和IRAK4是否参与Vogt-Koyanagi-Harada （VKH）病的发病机制。方法选取39例VKH患者和32例健康对照。采用实时定量PCR检测活动性VKH患者、非活动性VKH患者和正常人外周血单个核细胞（PBMCs）中IRAK1和IRAK4 mRNA水平。CD4+T细胞从活动性VKH患者和正常对照的pbmc中纯化。采用改良的MTT法测定IRAK1/4抑制IL-18或IL-1β刺激后CD4+T细胞增殖的影响。采用流式细胞术（FCM）和酶联免疫吸附法（ELISA）检测CD4+T细胞中IFN-γ和IL-17的表达。流式细胞术检测IRAK1/4抑制对NF-κB、STAT1、STAT3活化的影响。结果与非活动性VKH患者和健康对照相比，活动性VKH患者IRAK1和IRAK4 mRNA水平均显著升高。在不活跃的患者和健康对照组之间，IRAK1或IRAK4 mRNA水平未检测到差异。与IRAK1/4抑制剂孵育后，CD4+T细胞的增殖在活动性VKH患者和健康对照中均受到抑制。IRAK1/4抑制也与IFN-γ和IL-17的表达降低有关。抑制IRAK1/4后，健康对照CD4+T中NF-κB、STAT1和STAT3的磷酸化水平显著降低。结论IRAK1和IRAK4 mRNA高表达与VKH疾病活动性相关。IRAK1和IRAK4在CD4+T细胞的激活和增殖中发挥作用，在VKH中观察到的高表达可能有助于这种致盲疾病的发病机制。
Purpose To explore whether IRAK1 and IRAK4 are involved in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease. Methods Thirty-nine VKH patients and thirty-two healthy controls were included in this study. The mRNA levels of IRAK1 and IRAK4 from active VKH patients, inactive VKH patients, and normal controls in peripheral blood mononuclear cells (PBMCs) were detected using real-time quantitative PCR. CD4+T cells were purified from PBMCs obtained from active VKH patients and normal controls. The effect of IRAK1/4 inhibition on CD4+T cell proliferation following stimulation with IL-18 or IL-1β was measured using a modified MTT assay. CD4+T cell expression of IFN-γ and IL-17 were detected by flow cytometry (FCM) and enzyme-linked immunosorbent assay (ELISA). The effect of IRAK1/4 inhibition on NF-κB, STAT1, and STAT3 activation was detected by FCM. Results The mRNA levels of IRAK1 and IRAK4 were both significantly increased in active VKH patients compared to inactive VKH patients and healthy controls. No difference in the IRAK1 or IRAK4 mRNA level could be detected between inactive patients and healthy controls. After incubation with IRAK1/4 inhibitor, the proliferation of CD4+T cells was inhibited both in the active VKH patients and in the healthy controls. IRAK1/4 inhibition was also associated with a decreased expression of IFN-γ and IL-17. Phosphorylation of NF-κB, STAT1, and STAT3 in CD4+T from healthy controls was significantly decreased after inhibition of IRAK1/4. Conclusions High mRNA levels of IRAK1 and IRAK4 correlated with VKH disease activity. IRAK1 and IRAK4 play a role in the activation and proliferation of CD4+T cells and the higher expression observed in VKH may contribute to the pathogenesis of this blinding condition.
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影响因子：
56.9
作者：
Cao, ZD;Henzel, WJ;Gao, XO
通讯作者：
Gao, XO
DOI：
10.1073/pnas.0902745106
发表时间：
2009-04-28
影响因子：
11.1
作者：
Ben-Sasson, Shlomo Z.;Hu-Li, Jane;Paul, William E.
通讯作者：
Paul, William E.
影响因子：
4.1
作者：
Li, B;Yang, P;Kijlstra, A
通讯作者：
Kijlstra, A
影响因子：
5.5
作者：
Haseeb, Abdul;Chen, Dongxing;Haqqi, Tariq M.
通讯作者：
Haqqi, Tariq M.
影响因子：
13.7
作者：
Rao NA;Gupta A;Dustin L;Chee SP;Okada AA;Khairallah M;Bodaghi B;Lehoang P;Accorinti M;Mochizuki M;Prabriputaloong T;Read RW
通讯作者：
Read RW