Department of Internal Medicine, University of Pisa - School of Medicine, Via Roma 67, I-56100 Pisa, Italy.
Mol Cell Endocrinol. 2012 Feb 26;349(2):255-61. doi: 10.1016/j.mce.2011.11.001. Epub 2011 Nov 12.
Peroxisome proliferator-activated receptors (PPAR)α have been shown to exert immunomodulatory effects in autoimmune disorders; no study evaluated the effect of PPARα activation in Graves' ophthalmopathy (GO). We show the presence of PPARα, δ and γ in GO fibroblasts and preadipocytes. PPARα activators have a potent inhibitory action on the secretion of CXCL9 and CXCL11 chemokines (induced by IFNγ and TNFα) in fibroblasts and preadipocytes. The potency of the used PPARα agonists was maximum on the secretion of CXCL11 (67% inhibition by fenofibrate) in fibroblasts. The relative potency of the compounds in GO fibroblasts was different with each chemokine. PPARα agonists were stronger inhibitors of CXCL9 and CXCL11 (in GO fibroblasts and preadipocytes) than PPARγ activators. This study first shows that PPARα activators inhibit CXCL9 and CXCL11 chemokines in normal and GO fibroblasts and preadipocytes, suggesting that PPARα may be involved in the modulation of the immune response in GO.
过氧化物酶体增殖物激活受体 (PPAR)α 已被证明在自身免疫性疾病中具有免疫调节作用；尚无研究评估 PPARα 激活对格雷夫斯眼病 (GO) 的影响。我们显示 GO 成纤维细胞和前脂肪细胞中存在 PPARα、δ 和 γ。PPARα 激动剂对成纤维细胞和前脂肪细胞中由 IFNγ 和 TNFα 诱导的 CXCL9 和 CXCL11 趋化因子的分泌具有强大的抑制作用。在成纤维细胞中，所用的 PPARα 激动剂对 CXCL11 的抑制作用最强（fenofibrate 抑制 67%）。化合物在 GO 成纤维细胞中的相对效力因每种趋化因子而异。PPARα 激动剂对 CXCL9 和 CXCL11（在 GO 成纤维细胞和前脂肪细胞中）的抑制作用强于 PPARγ 激动剂。这项研究首次表明，PPARα 激动剂抑制正常和 GO 成纤维细胞和前脂肪细胞中的 CXCL9 和 CXCL11 趋化因子，提示 PPARα 可能参与 GO 中免疫反应的调节。
