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 (GlcN) on PAF-induced cellular activation in human HMO6 microglial cells. PAF induced sustained intracellular Ca(2+) ([Ca(2+)]i) increase through store-operated Ca(2+) channels (SOC) and reactive oxygen species (ROS) generation. PAF also induced pro-inflammatory markers through NFκB/COX-2 signaling. GlcN significantly inhibited PAF-induced Ca(2+) influx and ROS generation without significant cytotoxicity. GlcN downregulated excessive expression of pro-inflammatory markers and promoted filopodia formation through NFκB/COX-2 inhibition in PAF-stimulated HMO6 cells. Taken together, these data suggest that GlcN may offer substantial therapeutic potential for treating inflammatory and neurodegenerative diseases accompanied by microglial activation.
['Park|Jae-Hyung|JH|', 'Kim|Jeong-Nam|JN|', 'Jang|Byeong-Churl|BC|', 'Im|Seung-Soon|SS|', 'Song|Dae-Kyu|DK|', 'Bae|Jae-Hoon|JH|']
D002118:Calcium D020013:Calcium Signaling D002136:Calcium, Dietary D002478:Cells, Cultured D051546:Cyclooxygenase 2 D005944:Glucosamine D006801:Humans D017628:Microglia D010972:Platelet Activating Factor
Glucosamine Microglia Platelet-activating factor Intracellular calcium concentration Store-operated calcium channel