Microglia produce and hydrolyze palmitoylethanolamide

Microglial cell activation and migration play an important role in neuroinflammation propagation. While it is known that the lipid transmitter palmitoylethanolamide (PEA) regulates microglial migration by interacting with a cannabinoid-like receptor, the production and inactivation of this lipid by microglia has never been addressed directly. Here we show that the mouse microglial cell line BV-2 produces and hydrolyzes PEA. The carbamate compound URB602 inhibits PEA hydrolysis in BV-2 cell homogenates and increases PEA levels in intact cells, whereas the FAAH inhibitor URB597 and serine-hydrolase inhibitor MAFP do not affect PEA levels in intact cells. This unique pharmacological profile of inhibitors on PEA hydrolysis suggests the involvement of a previously undescribed enzyme that degrades PEA. This enzyme expressed by microglia constitutes a promising target for controlling the propagation of neuroinflammation.