Department of Dermatology, School of Medicine, Zhong Da Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
Mol Med Rep. 2020 Oct;22(4):3111-3116. doi: 10.3892/mmr.2020.11403. Epub 2020 Aug 3.
The present study aimed to investigate the role of janus kinase (JAK)1/STAT1 in interferon (IFN)‑γ‑induced apoptosis in human melanocytes. Following IFN‑γ treatment, the viability of human melanocytes were analyzed using a Cell Counting Kit‑8 assay and the apoptotic rate was determined using flow cytometry. Western blotting was also performed to analyze the phosphorylation levels of JAK1, JAK2 and the transcriptional factor STAT1, as well as the expression levels of Bcl‑2, Bax, Bcl‑2 homologous antagonist killer (Bak) and cleaved caspase‑3. Finally, following the pretreatment with the STAT1 inhibitor fludarabine, human melanocytes were treated with IFN‑γ and flow cytometry was used to detect the apoptotic rate. The results revealed that IFN‑γ reduced the proliferation and induced the apoptosis of human melanocytes. In addition, IFN‑γ treatment led to decreased expression levels of Bcl‑2 and increased expression levels of Bax, Bak and cleaved caspase‑3, alongside the activation of the JAK1/STAT1 signaling pathway. Conversely, the pretreatment with the STAT1 inhibitor fludarabine decreased the apoptotic rate of human melanocytes following IFN‑γ induction. In conclusion, the findings of the present study suggested that IFN‑γ may induce the apoptosis of human melanocytes by activating the JAK1/STAT1 signaling pathway, alongside increasing the expression levels of Bax, Bak and cleaved caspase‑3, and decreasing the expression levels of Bcl‑2.
本研究旨在探讨 Janus 激酶（JAK）1/STAT1 在干扰素（IFN）-γ诱导人黑素细胞凋亡中的作用。用细胞计数试剂盒-8 法分析 IFN-γ处理后人黑素细胞的活力，用流式细胞术测定细胞凋亡率。Western blot 法分析 JAK1、JAK2 和转录因子 STAT1 的磷酸化水平，以及 Bcl-2、Bax、Bcl-2 同源拮抗剂杀伤（Bak）和裂解的 caspase-3 的表达水平。最后，用 STAT1 抑制剂氟达拉滨预处理后，用 IFN-γ处理人黑素细胞，用流式细胞术检测细胞凋亡率。结果表明，IFN-γ降低了人黑素细胞的增殖并诱导其凋亡。此外，IFN-γ处理导致 Bcl-2 表达水平降低，Bax、Bak 和裂解的 caspase-3 表达水平升高，同时激活了 JAK1/STAT1 信号通路。相反，用 STAT1 抑制剂氟达拉滨预处理后，IFN-γ诱导的人黑素细胞凋亡率降低。综上所述，本研究结果提示 IFN-γ可能通过激活 JAK1/STAT1 信号通路，增加 Bax、Bak 和裂解的 caspase-3 的表达水平，降低 Bcl-2 的表达水平，诱导人黑素细胞凋亡。
