Abstract
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.
Highlights
Bee venom (BV) is a complex substance extracted from the honeybee (Apis mellifera L.) which contains a variety of enzymes, biologically active amines, peptides, and non-peptide components.The two major compounds in BV are melittin and phospholipase A2
To elucidate the regulatory mechanisms of BV are melittin and phospholipase A2 (bvPLA2) in Treg induction, we examined the role of apoptotic signaling during bvPLA2 treatment using splenocyte cultures.weThe mTOR the inhibitor
To elucidate the regulatory mechanisms of bvPLA2 in Treg induction, examined role of rapamycin was used as positive control in this study since it promotes the in vitro expansion of apoptotic signaling during bvPLA2 treatment using splenocyte cultures
Summary
Bee venom (BV) is a complex substance extracted from the honeybee (Apis mellifera L.) which contains a variety of enzymes, biologically active amines, peptides, and non-peptide components. The two major compounds in BV are melittin and phospholipase A2 (bvPLA2). Melittin is a cationic cell-lytic peptide consisting of 26 amino acids, and bvPLA2 is an enzyme which hydrolyzes membrane phospholipids. Bee venom therapy (BVT) consists in using BV for therapeutic purposes via injection by either stings from live bees or acupuncture needles. BVT has recently been widely used as an alternative therapy for the clinical treatment of a number of diseases, including rheumatoid arthritis. Toxins 2020, 12, 198 and Parkinson’s disease (PD) [1,2]. The anti-apoptosis, anti-fibrosis, and anti-inflammatory effects of BVT have been known for centuries and demonstrated in several reports and research articles [3,4,5]
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