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

Abstract

Microglia activation and subsequent release of inflammatory mediators are implicated in the pathophysi-ology of neurodegenerative diseases. Platelet-activating factor (PAF), a potent lipid mediator synthesizedby microglia, is known to stimulate microglia functional responses. In this study, we determined thatendogenous PAF exert autocrine effects on microglia activation, as well as the underlying mechanisminvolved. We also investigated the effect of d-glucosamine (GlcN) on PAF-induced cellular activationin human HMO6 microglial cells. PAF induced sustained intracellular Ca2+([Ca2+]i) increase throughstore-operated Ca2+channels (SOC) and reactive oxygen species (ROS) generation. PAF also induced pro-inflammatory markers through NF B/COX-2 signaling. GlcN significantly inhibited PAF-induced Ca2+influx and ROS generation without significant cytotoxicity. GlcN downregulated excessive expression ofpro-inflammatory markers and promoted filopodia formation through NF B/COX-2 inhibition in PAF-stimulated HMO6 cells. Taken together, these data suggest that GlcN may offer substantial therapeuticpotential for treating inflammatory and neurodegenerative diseases accompanied by microglial activa-tion.