Phospholipase A2 from Bee Venom Increases Poly(I:C)-induced Activation in Human Keratinocytes

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 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 phospholipase A2 (PLA2), 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-kappaB) and mitogen-activated protein kinases (MAPKs), and poly(I:C)-mediated IL-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.