Oh Jin-Gyo, Hwang Da-Jeong, Heo Tae-Hwe
Lab of Pharmaco-Immunology, Integrated Research Institute of Pharmaceutical Sciences, BK21 PLUS Team for Creative Leader Program for Pharmacomics-based Future Pharmacy, College of Pharmacy, The Catholic University of Korea, Bucheon 420-743, Republic of Korea.
Lab of Pharmaco-Immunology, Integrated Research Institute of Pharmaceutical Sciences, BK21 PLUS Team for Creative Leader Program for Pharmacomics-based Future Pharmacy, College of Pharmacy, The Catholic University of Korea, Bucheon 420-743, Republic of Korea; ILAb Inc., NP513, College of Pharmacy, The Catholic University of Korea, Bucheon 420-743, Republic of Korea.
Biochem Biophys Res Commun. 2018 Jan 1;495(1):300-305. doi: 10.1016/j.bbrc.2017.11.039. Epub 2017 Nov 7.
Interleukin-2 (IL-2) is a crucial growth factor for both regulatory and effector T cells. Thus, IL-2 plays a critical role in the stimulation and suppression of immune responses. Recently, anti-IL-2 antibodies (Abs) have been shown to possess strong IL-2 modulatory activities by affecting the interaction between IL-2 and IL-2 receptors. In this study, we screened an herbal library to identify a compound that regulates IL-2, which resulted in the identification of curcumin as a direct binder and inhibitor of IL-2. Curcumin is a phytochemical with well-known anti-cancer properties. In this study, curcumin mimicked or altered the binding pattern of anti-IL-2 Abs against IL-2 and remarkably inhibited the interaction of recombinant IL-2 with the IL-2 receptor α, CD25. Interestingly, curcumin neutralized the biological activities of IL-2 both in vitro and in vivo. In this report, we elucidated the unsolved mechanism of the anti-cancer effect of curcumin by identifying IL-2 as a direct molecular target. Curcumin, as a small molecule IL-2 modulator, has the potential to be used to treat IL-2 related pathologic conditions.
白细胞介素-2（IL-2）是调节性T细胞和效应T细胞的关键生长因子。因此，IL-2在免疫反应的刺激和抑制中起着关键作用。最近，抗IL-2抗体（Abs）已被证明通过影响IL-2与IL-2受体之间的相互作用而具有强大的IL-2调节活性。在本研究中，我们筛选了一个草药文库以鉴定一种调节IL-2的化合物，结果确定姜黄素是IL-2的直接结合剂和抑制剂。姜黄素是一种具有众所周知的抗癌特性的植物化学物质。在本研究中，姜黄素模拟或改变了抗IL-2抗体与IL-2的结合模式，并显著抑制重组IL-2与IL-2受体α（CD25）的相互作用。有趣的是，姜黄素在体外和体内均中和了IL-2的生物学活性。在本报告中，我们通过将IL-2鉴定为直接分子靶点，阐明了姜黄素抗癌作用的未解机制。姜黄素作为一种小分子IL-2调节剂，有潜力用于治疗与IL-2相关的病理状况。
