Altered AKT1 and MAPK1 gene expression on peripheral blood mononuclear cells and correlation with T-helper-transcription factors in systemic lupus erythematosus patients.

Altered AKT1 and MAPK1 gene expression on peripheral blood mononuclear cells and correlation with T-helper-transcription factors in systemic lupus erythematosus patients.
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DOI:
10.1155/2012/495934
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发表时间:
2012
影响因子:
4.6
通讯作者:
Zubiaur M
Zubiaur M
中科院分区:
医学3区
文献类型:
--
作者:
Garcia-Rodriguez S;Callejas-Rubio JL;Ortego-Centeno N;Zumaquero E;Ríos-Fernandez R;Arias-Santiago S;Navarro P;Sancho J;Zubiaur M

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激酶与系统性红斑狼疮(SLE)的免疫病理机制有关。采用实时定量逆转录聚合酶链反应检测了13例SLE患者外周血单个核细胞中v-akt鼠胸腺瘤病毒癌基因同源物1(AKT 1)和丝裂原活化蛋白激酶1(MAPK 1)基因的表达,并分析其与辅助性T细胞(Th)转录因子(TF)基因表达、细胞因子、和S100 A8/S100 A9-(钙卫蛋白)。年龄和性别匹配的13名健康对照进行了检查。AKT 1和MAPK 1在SLE患者中表达上调,并与Th 17-(视黄酸相关孤儿受体(ROR)-C)、T调节性(Treg)-(转化生长因子β(TGFB)-2)和Th 2-(白细胞介素(IL)-5)相关基因相关。MAPK 1表达与Th 1-(IL-12 A,T-box TF-(T-bet))、Th 2-(加塔结合蛋白-(加塔)-3)和IL-10表达相关。IL-10表达增加,并与血浆肿瘤坏死因子(TNF)-α和Th 0-(IL-2)、Th 1-(IL-12 A、T-bet)、GATA 3、Treg-(叉头/翼状螺旋转录因子-(FOXP)-3)和IL-6表达相关。FOXP 3表达、FOXP 3/RORC和FOXP 3/GATA 3表达比率增加。血浆IL-1β、IL-12(p70)、干扰素-(IFN)-γ和IL-6细胞因子增加。血浆IL-1β、IL-6、IL-2、IFN-γ、TNF-α、IL-10和IL-13分别与C-反应蛋白相关。钙卫蛋白增加与中性粒细胞相关。结论:SLE患者存在全身性免疫炎症活动,AKT 1、MAPK 1、促炎细胞因子和钙卫蛋白表达增加,Treg相关基因表达增加,提示调节反馈对抗炎症活动。
Kinases have been implicated in the immunopathological mechanisms of Systemic Lupus Erythematosus (SLE). v-akt murine-thymoma viral-oncogene-homolog 1 (AKT1) and mitogen-activated-protein-kinase 1 (MAPK1) gene expressions in peripheral mononuclear cells from thirteen SLE patients with inactive or mild disease were evaluated using quantitative real-time reverse-transcription polymerase-chain-reaction and analyzed whether there was any correlation with T-helper (Th) transcription factors (TF) gene expression, cytokines, and S100A8/S100A9-(Calprotectin). Age- and gender-matched thirteen healthy controls were examined. AKT1 and MAPK1 expressions were upregulated in SLE patients and correlated with Th17-(Retinoic acid-related orphan receptor (ROR)-C), T-regulatory-(Treg)-(Transforming Growth Factor Beta (TGFB)-2), and Th2-(interleukin (IL)-5)-related genes. MAPK1 expression correlated with Th1-(IL-12A, T-box TF-(T-bet)), Th2-(GATA binding protein-(GATA)-3), and IL-10 expressions. IL-10 expression was increased and correlated with plasma Tumor Necrosis Factor (TNF)-α and Th0-(IL-2), Th1-(IL-12A, T-bet), GATA3, Treg-(Forkhead/winged-helix transcription factor- (FOXP)-3), and IL-6 expressions. FOXP3 expression, FOXP3/RORC, and FOXP3/GATA3 expression ratios were increased. Plasma IL-1β, IL-12(p70), Interferon-(IFN)-γ, and IL-6 cytokines were augmented. Plasma IL-1β, IL-6, IL-2, IFN-γ, TNF-α, IL-10, and IL-13 correlated with C-reactive protein, respectively. Increased Calprotectin correlated with neutrophils. Conclusion, SLE patients presented a systemic immunoinflammatory activity, augmented AKT1 and MAPK1 expressions, proinflammatory cytokines, and Calprotectin, together with increased expression of Treg-related genes, suggesting a regulatory feedback opposing the inflammatory activity.
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使用基于途径的方法对微阵列数据进行荟萃分析确定了人类外周血单核细胞中全身性红斑狼疮的37基因表达签名。
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