Department of Internal Medicine, University of Pisa, School of Medicine, Via Roma 67, Pisa, Italy.
Cytokine. 2010 Jun;50(3):260-7. doi: 10.1016/j.cyto.2010.01.009. Epub 2010 Mar 17.
It has been hypothesized that interferon (IFN) alpha and beta cause autoimmune thyroid dysfunctions by changing the Th1/Th2 balance, but the mechanisms involved are not yet known. The aims of this study were: (a) to test the effect of IFNalpha, IFNbeta and IFNgamma on the secretion of the Th1 chemokines CXCL9 and CXCL10, in "primary cultures of human thyroid follicular cells" (TFC); (b) to assess the effect of PPARgamma activation on CXCL9 and CXCL10 secretion. In TFC, CXCL9 and CXCL10 were undetectable in the supernatant. IFNgamma, IFNalpha and IFNbeta, dose dependently induced CXCL9 and CXCL10 release. TNFalpha alone had no effect. The combination of each of the IFNs with TNFalpha had a significant synergistic effect on CXCL9 and CXCL10 secretion. Treatment of TFC with rosiglitazone dose dependently inhibited the IFNs-stimulated CXCL9 and CXCL10 release. Compared with IFNalpha and IFNbeta, IFNgamma was the most potent stimulus of CXCL9 and CXCL10 secretion. In conclusion, IFNalpha, IFNbeta, IFNgamma and TNFalpha (synergistically with IFNs) dose-dependently induce the release of CXCL9 and CXCL10 by TFC, suggesting that this process may be related, at least in part, to the appearance of thyroid dysfunction during IFNs therapy. Furthermore, PPARgamma activation partially inhibits this process.
据推测，干扰素 (IFN)α 和β通过改变 Th1/Th2 平衡导致自身免疫性甲状腺功能障碍，但涉及的机制尚不清楚。本研究的目的是：(a) 检测 IFNα、IFNβ 和 IFNγ 对“人甲状腺滤泡细胞原代培养物”(TFC)中 Th1 趋化因子 CXCL9 和 CXCL10 分泌的影响；(b) 评估过氧化物酶体增殖物激活受体 γ(PPARγ)激活对 CXCL9 和 CXCL10 分泌的影响。在 TFC 中，上清液中无法检测到 CXCL9 和 CXCL10。IFNγ、IFNα 和 IFNβ 呈剂量依赖性诱导 CXCL9 和 CXCL10 释放。TNFα 单独作用无影响。IFN 与 TNFα 的组合对 CXCL9 和 CXCL10 的分泌具有显著协同作用。罗格列酮治疗 TFC 呈剂量依赖性抑制 IFN 刺激的 CXCL9 和 CXCL10 释放。与 IFNα 和 IFNβ 相比，IFNγ 是刺激 CXCL9 和 CXCL10 分泌的最有效刺激物。总之，IFNα、IFNβ、IFNγ 和 TNFα(与 IFN 协同作用)呈剂量依赖性诱导 TFC 释放 CXCL9 和 CXCL10，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。此外，PPARγ 激活部分抑制了这一过程。
