CXCL9 and CXCL11 Chemokines Modulation by Peroxisome Proliferator-Activated Receptor-α Agonists Secretion in Graves' and Normal Thyrocytes
CXCL9 and CXCL11 Chemokines Modulation by Peroxisome Proliferator-Activated Receptor-α Agonists Secretion in Graves' and Normal Thyrocytes
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DOI：
10.1210/jc.2010-0923
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发表时间：
2010-12-01
影响因子：
5.8
通讯作者：
Fallahi, Poupak
中科院分区：
文献类型：
--
作者：
Antonelli, Alessandro;Ferrari, Silvia Martina;Fallahi, Poupak
背景：过氧化物酶体增殖激活受体(PPAR)- α已被证明在自身免疫性疾病中发挥免疫调节作用。然而，到目前为止，文献中还没有关于PPAR α激活对CXCL9和CXCL11趋化因子的一般影响或对甲状腺细胞中这些趋化因子分泌的影响的数据。目的与设计：采用实时荧光定量pcr技术检测Graves病（GD）和对照细胞中PPAR α和PPAR γ的含量。此外，我们通过IFN γ和TNF α刺激趋化因子分泌后，测试了PPAR α和PPAR γ活化对GD和对照细胞中CXCL9和CXCL11分泌的作用。结果：本研究显示PPAR α和PPAR γ在GD和对照细胞中存在。在GD和对照细胞中，PPAR α激动剂对细胞因子刺激的CXCL9和CXCL11分泌有明显的剂量依赖性抑制作用。所使用的PPAR α激动剂对CXCL9分泌的抑制作用最大，非诺贝特和环丙贝特的抑制作用分别达到90%和85%。各趋化因子的相对效价不同；例如，gemfibrozil对CXCL11的抑制作用为55%，而对CXCL9的抑制作用较弱（40%）。PPAR α激动剂对甲状腺细胞中CXCL9和CXCL11分泌的抑制作用强于PPAR γ激动剂（方差分析，P < 0.001）。结论：我们的研究表明PPAR α存在于GD和对照甲状腺细胞中。PPAR α激活剂是CXCL9和CXCL11分泌的有效抑制剂，提示PPAR α可能参与甲状腺免疫反应的调节。[J] .中华内分泌杂志，2010,31(5):563 - 568。
Context: Peroxisome proliferator-activated receptor (PPAR)-alpha has been shown to exert immunomodulatory effects in autoimmune disorders. However, until now, no data were present in the literature about the effect of PPAR alpha activation on CXCL9 and CXCL11 chemokines in general or on secretion of these chemokines in thyroid cells.Objective and Design: The presence of PPAR alpha and PPAR gamma has been evaluated by real-time-PCR in Graves' disease (GD) and control cells in primary culture. Furthermore, we have tested the role of PPAR alpha and PPAR gamma activation on CXCL9 and CXCL11 secretion in GD and control cells after stimulation of these chemokines secretion with IFN gamma and TNF alpha.Results: This study shows the presence of PPAR alpha and PPAR gamma in GD and control cells. A potent dose-dependent inhibition by PPAR alpha-agonists was observed on the cytokines-stimulated secretion of CXCL9 and CXCL11 in GD and control cells. The potency of the PPAR alpha agonists used was maximum on the secretion of CXCL9, reaching about 90% of inhibition by fenofibrate and 85% by ciprofibrate. The relative potency of the compounds was different with each chemokine; for example, gemfibrozil exerted a 55% inhibition on CXCL11, whereas it had a weaker activity on CXCL9 (40% inhibition). PPAR alpha agonists were stronger (ANOVA, P < 0.001) inhibitors of CXCL9 and CXCL11 secretion in thyrocytes than PPAR gamma agonists.Conclusions: Our study shows the presence of PPAR alpha in GD and control thyrocytes. PPAR alpha activators are potent inhibitors of the secretion of CXCL9 and CXCL11, suggesting that PPAR alpha may be involved in the modulation of the immune response in the thyroid. (J Clin Endocrinol Metab 95: E413-E420, 2010)