Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea.
Department of Anatomy and Acupoint, College of Korean Medicine, Gachon University, Seongnam 13120, Korea.
Toxins (Basel). 2020 Mar 22;12(3):198. doi: 10.3390/toxins12030198.
Bee venom phospholipase A2 is a lipolytic enzyme in bee venom that catalyzes hydrolysis of the sn-2 ester bond of membrane phospholipids to produce free fatty acid and lysophospholipids. Current evidence suggests that bee venom phospholipase A2 (bvPLA2) induces regulatory T cell expansion and attenuates several immune system-related diseases, including Alzheimer's disease. The induction of Treg cells is directly mediated by binding to mannose receptors on dendritic cells. This interaction induces the PGE2-EP2 signaling pathway, which promotes Treg induction in CD4 T cells. In this study, we investigated the effects of bvPLA2 treatment on the apoptotic signaling pathway in Treg populations. Flow cytometry was performed to identify early apoptotic cells. As a result, early apoptotic cells were dramatically decreased in bvPLA2-treated splenocytes, whereas rapamycin-treated cells showed levels of apoptotic cells similar to those of PBS-treated cells. Furthermore, bvPLA2 treatment increased expression of anti-apoptotic molecules including CTLA-4 and PD-1. The survival rate increased in bvPLA2-treated Tregs. Our findings indicate that bvPLA2-mediated modulation of apoptotic signaling is strongly associated with the Treg induction, which exhibits protective effects against various immune-related diseases. To our knowledge, this study is the first to demonstrate that bvPLA2 is the major bee venom (BV) compound capable of inducing Treg expansion through altering apoptotic signal.
蜂毒磷脂酶 A2 是蜂毒中的一种脂解酶，可催化膜磷脂 sn-2 酯键的水解，生成游离脂肪酸和溶血磷脂。现有证据表明，蜂毒磷脂酶 A2（bvPLA2）可诱导调节性 T 细胞扩增，并减轻几种与免疫系统相关的疾病，包括阿尔茨海默病。Treg 细胞的诱导是通过与树突状细胞上的甘露糖受体直接结合介导的。这种相互作用诱导 PGE2-EP2 信号通路，促进 CD4 T 细胞中 Treg 的诱导。在这项研究中，我们研究了 bvPLA2 处理对 Treg 群体中细胞凋亡信号通路的影响。通过流式细胞术鉴定早期凋亡细胞。结果表明，bvPLA2 处理的脾细胞中早期凋亡细胞明显减少，而雷帕霉素处理的细胞中凋亡细胞水平与 PBS 处理的细胞相似。此外，bvPLA2 处理增加了包括 CTLA-4 和 PD-1 在内的抗凋亡分子的表达。bvPLA2 处理的 Treg 的存活率增加。我们的研究结果表明，bvPLA2 介导的凋亡信号调节与 Treg 诱导强烈相关，这显示了对各种与免疫相关的疾病的保护作用。据我们所知，这项研究首次表明，bvPLA2 是通过改变凋亡信号来诱导 Treg 扩增的主要蜂毒（BV）化合物。
