Department of Internal Medicine, University of Pisa, School of Medicine, Via Roma 67, 56100 Pisa, Italy.
Immunobiology. 2013 May;218(5):690-5. doi: 10.1016/j.imbio.2012.08.267. Epub 2012 Aug 9.
It has been previously shown IFN-α, -β, -γ and TNF-α (synergically with IFNs) dose-dependently induce the release of CXCL9 and CXCL10 chemokines by thyroid follicular cells, suggesting that this process may be related, at least in part, to the appearance of thyroid dysfunction during IFNs therapy. No study has evaluated the effect of IFN-α and -β on CXCL11 chemokine production in thyrocytes. The aims of this study were: (a) to test the effect of IFN-α, -β and -γ on the secretion of the Th1 chemokine CXCL11, in primary cultures of human thyroid follicular cells; (b) to assess the effect of PPAR-γ activation on CXCL11 secretion. In primary cultures of human thyroid follicular cells, CXCL11 was undetectable in the supernatant. IFN-γ, -α and -β dose dependently induced CXCL11 release. TNF-α alone had no effect. The combination of each of the IFNs with TNF-α had a significant synergistic effect on CXCL11 secretion. Treatment of primary cultures of human thyroid follicular cells with rosiglitazone dose dependently inhibited the IFNs stimulated CXCL11 release. Compared with IFN-α and -β, IFN-γ was the most potent stimulus of CXCL11 secretion. In conclusion, we first show that IFN-α, -β and -γ and TNF-α (synergically with IFNs) dose-dependently induce the release of CXCL11 by primary cultures of human thyroid follicular cells, suggesting that this process may be related to the appearance of thyroid dysfunction during IFNs therapy. Furthermore, PPAR-γ activation partially inhibits this process.
先前的研究表明，IFN-α、-β、-γ 和 TNF-α（与 IFNs 协同作用）剂量依赖性地诱导甲状腺滤泡细胞释放 CXCL9 和 CXCL10 趋化因子，这表明该过程至少部分与 IFN 治疗期间甲状腺功能障碍的出现有关。尚无研究评估 IFN-α 和 -β 对甲状腺细胞中 CXCL11 趋化因子产生的影响。本研究的目的是：（a）检测 IFN-α、-β 和 -γ 对人甲状腺滤泡细胞原代培养物中 Th1 趋化因子 CXCL11 分泌的影响；（b）评估 PPAR-γ 激活对 CXCL11 分泌的影响。在人甲状腺滤泡细胞原代培养物中，上清液中未检测到 CXCL11。IFN-γ、-α 和 -β 剂量依赖性地诱导 CXCL11 释放。TNF-α 单独使用时没有效果。IFN-α、-β 和 -γ 与 TNF-α 联合使用对 CXCL11 分泌有显著的协同作用。用罗格列酮处理人甲状腺滤泡细胞原代培养物，可剂量依赖性地抑制 IFNs 刺激的 CXCL11 释放。与 IFN-α 和 -β 相比，IFN-γ 是刺激 CXCL11 分泌最有效的刺激物。总之，我们首次表明，IFN-α、-β 和 -γ 以及 TNF-α（与 IFNs 协同作用）可剂量依赖性地诱导人甲状腺滤泡细胞原代培养物释放 CXCL11，提示该过程可能与 IFN 治疗期间甲状腺功能障碍的出现有关。此外，PPAR-γ 激活部分抑制了这一过程。
