Ning Weixuan, Wang Suiquan, Dong Xiaowu, Liu Dongyin, Fu Lifang, Jin Rong, Xu Aie
Department of Dermatology, Guangxing Affiliated Hospital of Zhejiang Chinese Medical University.
Biol Pharm Bull. 2015;38(11):1700-6. doi: 10.1248/bpb.b15-00331. Epub 2015 Sep 4.
Vitiligo is an inflammatory skin disorder in which activated T cells play an important role in its onset and progression. Epigallocatechin-3-gallate (EGCG), the major chemical constituent of green tea, exhibits remarkable anti-oxidative and anti-inflammatory properties. EGCG administration has been confirmed to decrease the risk of vitiligo; however, the underlying mechanism is undetermined. In this study, we proved that EGCG directly inhibited the kinase activity of Janus kinase 2 (JAK2). In primary cultured human melanocytes, EGCG pre-treatment attenuated interferon (IFN)-γ-induced phosphorylation of JAK2 and its downstream signal transducer and activator of transcription (STAT)1 and STAT3 in a dose-dependent manner. We further examined the chemoattractant expression in melanocytes and demonstrated that EGCG significantly inhibited IFN-γ-induced expression of intracellular adhesion molecule (ICAM)-1, CXCL10, and monocyte chemotactic protein (MCP)-1 in human melanocytes. In addition, EGCG reduced the protein levels of the corresponding receptors including CD11a, CXCR3, and CCR2 in human T lymphocytes. As a consequence, adhesion of human T cells to melanocytes induced by IFN-γ was effectively suppressed by EGCG. Taken together, our results provided new evidence for the effectiveness of EGCG in vitiligo treatment and supported JAK2 as a molecular target for vitiligo medicine development.
白癜风是一种炎症性皮肤病,其中活化的T细胞在其发病和进展中起重要作用。表没食子儿茶素-3-没食子酸酯(EGCG)是绿茶的主要化学成分,具有显著的抗氧化和抗炎特性。已证实给予EGCG可降低患白癜风的风险;然而,其潜在机制尚不清楚。在本研究中,我们证明EGCG直接抑制Janus激酶2(JAK2)的激酶活性。在原代培养的人黑素细胞中,EGCG预处理以剂量依赖的方式减弱了干扰素(IFN)-γ诱导的JAK2及其下游信号转导子和转录激活子(STAT)1和STAT3的磷酸化。我们进一步检测了黑素细胞中的趋化因子表达,并证明EGCG显著抑制人黑素细胞中IFN-γ诱导的细胞间黏附分子(ICAM)-1、CXCL10和单核细胞趋化蛋白(MCP)-1的表达。此外,EGCG降低了人T淋巴细胞中包括CD11a、CXCR3和CCR2在内的相应受体的蛋白水平。因此,EGCG有效抑制了IFN-γ诱导的人T细胞与黑素细胞的黏附。综上所述,我们的结果为EGCG治疗白癜风的有效性提供了新证据,并支持JAK2作为白癜风药物开发的分子靶点。