Glucosamine suppresses platelet-activating factor-induced activation of microglia through inhibition of store-operated calcium influx

Microglia activation and subsequent release of inflammatory mediators are implicated in the pathophysiology of neurodegenerative diseases. Platelet-activating factor (PAF), a potent lipid mediator synthesized by microglia, is known to stimulate microglia functional responses. In this study, we determined that endogenous PAF exert autocrine effects on microglia activation, as well as the underlying mechanism involved. We also investigated the effect of D-glucosamine (GIcN) on PAF-induced cellular activation in human HMO6 microglial cells. PAF induced sustained intracellular Ca2+ ([Ca2+](i)) increase through store-operated Ca2+ channels (SOC) and reactive oxygen species (ROS) generation. PAF also induced pro inflammatory markers through NFKB/COX-2 signaling. GlcN significantly inhibited PAF-induced Ca2+ influx and ROS generation without significant cytotoxicity. GlcN downregulated excessive expression of pro-inflammatory markers and promoted filopodia formation through NFKB/COX-2 inhibition in PAF-stimulated HMO6 cells. Taken together, these data suggest that GIcN may offer substantial therapeutic potential for treating inflammatory and neurodegenerative diseases accompanied by microglial activation. (C) 2015 Elsevier B.V. All rights reserved.