Enhanced rho-associated protein kinase activation in patients with systemic lupus erythematosus.
Enhanced rho-associated protein kinase activation in patients with systemic lupus erythematosus.
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DOI：
10.1002/art.37934
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发表时间：
2013-06
影响因子：
--
通讯作者：
Pernis, Alessandra B.
中科院分区：
文献类型：
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作者：
Isgro, Josephine;Gupta, Sanjay;Jacek, Elzbieta;Pavri, Tanya;Duculan, Roland;Kim, Mimi;Kirou, Kyriakos A.;Salmon, Jane E.;Pernis, Alessandra B.
Rho激酶（ROCK）与心血管和肾脏疾病的发病机制有关。我们最近发现ROCKs可以调节小鼠TH17细胞的分化和IL-17和IL-21的产生，这两种细胞因子与SLE相关。本研究的目的是评估ROCK在人TH17细胞中的活化，并评估ROCK在SLE患者中的活性。采用基于ELISA的ROCK活性测定来评估在TH0或TH17条件下分化的人脐带血CD4 + T细胞中的ROCK活性。然后我们对28例SLE患者和25例健康对照进行了横断面分析。通过ELISA评估外周血单核细胞（PBMC）裂解物中的ROCK活性。通过ELISA分析细胞因子和趋化因子谱。在TH17条件下分化的人脐带血CD4 + T细胞比在TH0条件下刺激的CD4 + T细胞表达更高水平的ROCK活性。通过加入ROCK抑制剂进一步抑制IL-17和IL-21的产生。与健康对照相比，SLE PBMC表达显著更高水平的ROCK活性，分别为1.25对0.56（p = 0.0015）。16例（57%）SLE患者表达高水平ROCK（OD 450> 1）。在多变量分析中，疾病持续时间、淋巴细胞计数和硫唑嘌呤使用是ROCK活性的重要独立预测因素。与先前在鼠系统中的结果一致，增加的ROCK活化与TH17分化相关。此外，在SLE患者亚组中观察到ROCK活性增强。这些数据支持了ROCK通路可能是SLE的重要治疗靶点的概念。
Rho-kinases (ROCKs) have been implicated in the pathogenesis of cardiovascular and renal disorders. We recently showed that ROCKs could regulate the differentiation of murine TH17 cells and production of IL-17 and IL-21, two cytokines associated with SLE. The goal of this study was to assess ROCK activation in human TH17 cells and evaluate ROCK activity in SLE patients. An ELISA-based ROCK activity assay was employed to evaluate ROCK activity in human cord blood CD4+ T cells differentiated under TH0 or TH17 conditions. We then performed a cross-sectional analysis of 28 SLE patients and 25 healthy matched controls. ROCK activity in peripheral blood mononuclear cell (PBMC) lysates was assessed by ELISA. Cytokine and chemokine profiles were analyzed via ELISA. Human cord blood CD4+ T cells differentiated under TH17 conditions expressed higher levels of ROCK activity than CD4+ T cells stimulated under TH0 conditions. Production of IL-17 and IL-21 was furthermore inhibited by addition of a ROCK inhibitor. SLE PBMCs expressed significantly higher levels of ROCK activity as compared to healthy controls, 1.25 vs. 0.56, respectively (p=0.0015). Sixteen (57%) SLE patients expressed high ROCK levels (OD450>1). Disease duration, lymphocyte count, and azathioprine use were significant independent predictors of ROCK activity in multivariable analyses. Consistent with previous results in the murine system, increased ROCK activation was associated with TH17 differentiation. Enhanced ROCK activity was furthermore observed in a subgroup of SLE patients. These data support the concept that the ROCK pathway could represent an important therapeutic target for SLE.
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影响因子：
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作者：
Petri, Michelle;Stohl, William;Freimuth, William
通讯作者：
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通讯作者：
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