Bee Venom Phospholipase A2 Induces Regulatory T Cell Populations by Suppressing Apoptotic Signaling Pathway

被引:23
作者
Baek, Hyunjung [1 ]
Park, Seon-Young [1 ]
Ku, Su Jeong [2 ]
Ryu, Kihyun [1 ]
Kim, Younsub [2 ]
Bae, Hyunsu [1 ]
Lee, Ye-Seul [2 ]
机构
[1] Kyung Hee Univ, Coll Korean Med, Dept Physiol, Seoul 02447, South Korea
[2] Gachon Univ, Coll Korean Med, Dept Anat & Acupoint, Seongnam 13120, South Korea
基金
新加坡国家研究基金会;
关键词
bee venom phospholipase A2; bvPLA2; regulatory T cells; Tregs; apoptosis; DISEASE PROGRESSION; GENERATION; MODEL; INFLAMMATION; ACTIVATION; INDUCTION; TOLERANCE; RAPAMYCIN; DEATH;
D O I
10.3390/toxins12030198
中图分类号
TS2 [食品工业];
学科分类号
0832 ;
摘要
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.
引用
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页数:14
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