Bee venom (BV) induces skin inflammation, characterized by erythema, blisters, edemas, pain and itching. Although BV has been found to have an inhibitory effect on toll-like receptors (TLRs), we here show that BV enhances keratinocyte responses to polyinosinic-polycytidylic acid [poly(I:C)], a ligand for TLR3. Our results revealed that the enhanced TLR activity was primarily induced by secretory phospholipase A2 (sPLA2), a component of BV (BV-sPLA2). PLA2 mediates the hydrolysis of membrane phospholipids into lysophospholipids and free fatty acids. We demonstrated that BV-sPLA2 increased the intracellular uptake of poly(I:C), phosphorylation of the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs), and poly(I:C)-mediated interleukin 8 production in human keratinocytes. We further showed that the enzymatic activity of BV-sPLA2 was essential for the increased uptake of poly(I:C). These findings suggest that BV-sPLA2 may induce a modification of the cell membrane structure, leading to enhanced poly(I:C) uptake in keratinocytes. BV-sPLA2 might be able to promote wound healing by enhancing TLR3 responses.

中文翻译：

---

蜂毒中的磷脂酶A2增强了人角质形成细胞中poly（I：C）诱导的活化。

蜂毒（BV）引起皮肤炎症，特征是红斑，水泡，水肿，疼痛和瘙痒。尽管已发现BV对Toll样受体（TLR）有抑制作用，但我们在这里显示BV增强了对多肌苷酸-聚胞苷酸[poly（I：C）]（TLR3的配体）的角质形成细胞反应。我们的研究结果表明，增强的TLR活性主要是由分泌性磷脂酶A2（sPLA2）（BV的一种成分（BV-sPLA2））诱导的。PLA2介导膜磷脂水解为溶血磷脂和游离脂肪酸。我们证明BV-sPLA2增加了poly（I：C）的细胞内摄取，核因子-κB（NF-κB）和有丝分裂原激活的蛋白激酶（MAPKs）的磷酸化，以及poly（I：C）介导的人角质形成细胞中白介素8的产生。我们进一步表明BV-sPLA2的酶活性对于增加poly（I：C）的摄取至关重要。这些发现表明，BV-sPLA2可能诱导细胞膜结构的修饰，导致角质形成细胞中的聚（I：C）摄取增加。BV-sPLA2可能能够通过增强TLR3反应来促进伤口愈合。