ITE is an effective immunosuppressive endogenous aromatic hydrocarbon receptor (AhR) agonist, with a Ki value of 3nM for binding to AhR [1]. AhR is a ligand-dependent transcription factor that mediates the toxicity of several xenobiotics and plays important physiological roles in differentiation, reproduction, and immunity [2]. ITE has immunomodulatory and anti-cancer effects [3-4].
In vitro, ITE (0.1–5000nM; 1-6 days) treatment inhibited the proliferation and migration of ovarian cancer cells (SKOV-3, OVCAR-3, and IOSE-385) in a dose- and time-dependent manner, reduced AhR, and increased CYP1A1 levels [5]. ITE (0.01, 0.1, 1, 5, 10, and 20μM; 2, 4, or 6 days) could inhibit the proliferation of human pulmonary artery endothelial cells (HPAEC) in a dose- and time-dependent manner, reduced AhR protein levels, and simultaneously increased the mRNA levels of cytochrome P450 (CYP), CYP1A1, and CYP1B1 [6].
In vivo, ITE (200μg/0.2mL/day; 14 days; i.p.) treatment could significantly inhibit retinal detachment and ocular inflammatory cell infiltration in mice with experimental autoimmune uveitis (EAU) induced by Freund's adjuvant and Mycobacterium tuberculosis, reduced the proportion of IFN-γ, IL-17, or IL-10 cells in mice, and inhibited the secretion of inflammatory cytokines by mouse lymphocytes [7]. ITE (80mg/kg/day; 28 days; i.p.) treatment could reduce tumor growth by 39% in OVCAR-3 xenograft model mice [5].
References:
[1] Song J, et al. A ligand for the aryl hydrocarbon receptor isolated from lung. Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14694-9.
[2] Henry E C, Welle S L, Gasiewicz T A. TCDD and a putative endogenous AhR ligand, ITE, elicit the same immediate changes in gene expression in mouse lung fibroblasts[J]. Toxicological Sciences, 2010, 114(1): 90-100.
[3] Dolciami D, Gargaro M, Cerra B, et al. Binding mode and structure–activity relationships of ITE as an aryl hydrocarbon receptor (AhR) agonist[J]. ChemMedChem, 2018, 13(3): 270-279.
[4] Simpson S R, Middleton D D, Lukesh N R, et al. Microparticles incorporating dual apoptotic factors to inhibit inflammatory effects in macrophages[J]. Journal of Pharmaceutical Sciences, 2024, 113(11): 3196-3205.
[5] Wang K, Li Y, Jiang YZ, et al. An endogenous aryl hydrocarbon receptor ligand inhibits proliferation and migration of human ovarian cancer cells. Cancer Lett. 2013;340(1):63-71.
[6] Pang L, Li Y, Zou Q, et al. ITE inhibits growth of human pulmonary artery endothelial cells[J]. Experimental lung research, 2017, 43(8): 283-292.
[7] Nugent LF, Shi G, Vistica BP, Ogbeifun O, Hinshaw SJ, Gery I. ITE, a novel endogenous nontoxic aryl hydrocarbon receptor ligand, efficiently suppresses EAU and T-cell-mediated immunity. Invest Ophthalmol Vis Sci. 2013 Nov 13;54(12):7463-9.
ITE是一种有效的免疫抑制性内源性芳香烃受体（AhR）激动剂，与AhR结合的Ki值为3nM [1]。AhR是一种配体依赖性转录因子，介导几类异生素的毒性，并且在分化、繁殖和免疫中具有重要的生理作用 [2]。ITE具有免疫调节和抗癌作用 [3-4]。
在体外，ITE（0.1–5000Nm; 1-6 days）处理以剂量和时间依赖性抑制卵巢癌细胞（SKOV-3，OVCAR-3和IOSE-385）的增殖和迁移，降低AhR水平并增加CYP1A1水平 [5]。ITE（0.01, 0.1, 1, 5, 10 and 20μM; 2, 4, or 6 days）能够以剂量和时间依赖性抑制人肺动脉内皮细胞（HPAEC）的增殖，降低了AhR蛋白水平，同时增加了细胞色素P450（CYP）、CYP1A1和CYP1B1的mRNA水平 [6]。
在体内，ITE（200μg/0.2mL/day; 14 days; i.p.）治疗能够显著抑制弗氏佐剂（CFA）和结核分枝杆菌诱导的实验性自身免疫性葡萄膜炎（EAU）小鼠的视网膜脱离以及眼部炎症细胞浸润现象，降低小鼠IFN-γ、IL-17或IL-10的细胞比例，还抑制小鼠淋巴细胞分泌炎性细胞因子 [7]。ITE（80mg/kg/day; 28 days; i.p.）治疗能够使OVCAR-3异种移植模型小鼠中的肿瘤生长减少39% [5]。