ハチ毒由来PLA2の皮膚角化細胞における免疫応答への影響

抄録

 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 (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.