ITE

2-(1′H-吲哚-3′-羰基)-噻唑-4-甲酸甲酯(ITE)是无毒的免疫抑制性内源性芳香烃受体(AhR)的配体[1,2]。酵母AhR实验测定的EC50为7.8×10-10 M [3]。

AhR是转录因子，介导环境污染物如2，3，7，8-四氯二苯并对二恶英（TCDD）的毒性效应，由配体激活[2]。

在TGFβ1挑战的不同组织中分离的原代人成纤维细胞培养物中，ITE抑制TGFβ1诱导的肌成纤维细胞分化。在原代人眼眶成纤维细胞中，ITE抑制TGFβ1诱导的Smad2/3/4核转移及其随后结合到SBE，但是并不抑制TGFβ1诱导的Smad2/3、Erk1/2或Akt的磷酸化[4]，其抑制TGFβ1 (1 ng/ml)诱导的α-平滑肌肌动蛋白(α-SMA)表达和胞外基质产生[5]。ITE抑制TGFβ1诱导的人原代成纤维细胞中肌成纤维细胞分化是AhR非依赖性的[5]。

维持12小时光照/12小时黑暗循环的环境下，自由获得固态食物和无菌水的Sprague-Dawley大鼠按1.6和8.0 mg/kg给予ITE能显著提高CYP1A1 mRNA水平至5.59和68.55倍。表明胎盘中ITE激活AhR的活化。8.0 mg/kg ITE提高HIF-1α mRNA水平，以剂量依赖的方式诱导VEGF-A、VEGF-B和PIGF mRNA的水平[6]。

参考文献：
[1].  Lindsey F. Nugent, Guangpu Shi, Barbara P. Vistica, et al. ITE, A Novel Endogenous Nontoxic Aryl Hydrocarbon Receptor Ligand, Efficiently Suppresses EAU and T-Cell–Mediated Immunity. Invest Ophthalmol Vis Sci., 2013, 54(12):7463-7469.
[2].  Jaishree Bankoti, Ben Rase, Tom Simones, et al. Functional and phenotypic effects of AhR activation in inflammatory dendritic cells. Toxicol Appl Pharmacol., 2010, 246(1-2):18-28.
[3].  S. Medjakovic and A. Jungbauer. Red clover isoflavones biochanin A and formononetin are potent ligands of the human aryl hydrocarbon receptor. Journal of Steroid Biochemistry & Molecular Biology, 2008, 108:171-177.
[4].  Geniece M. Lehmann, Xia Xi, Ajit A. Kulkarni, et al. The Aryl Hydrocarbon Receptor Ligand ITE Inhibits TGFβ1-Induced Human Myofibroblast Differentiation. American Journal of Pathology, 2011, 178(4):1556–1567.
[5].  Geniece M. Lehmann, Xia Xi, Ajit A. Kulkarni, et al. The Aryl Hydrocarbon Receptor Ligand ITE Inhibits TGF1-Induced Human Myofibroblast Differentiation. The American Journal of Pathology, 2011, 178(4):1556-1567.
[6].  Yanming Wu, Xiao Chen, Qian Zhou, et al. ITE and TCDD Differentially Regulate the Vascular Remodeling of Rat Placenta via the Activation of AhR. PLoS ONE, 2014, 9(1): e86549.