title: 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 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.
authors.affiliation: Department of Physiology, Keimyung University School of Medicine, Daegu, South Korea.
authors.forename: Jae-Hyung
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Physiology, Keimyung University School of Medicine, Daegu, South Korea.
authors.forename: Jeong-Nam
authors.initials: JN
authors.lastname: Kim
authors.affiliation: Department of Molecular Medicine, Keimyung University School of Medicine, Daegu, South Korea.
authors.forename: Byeong-Churl
authors.initials: BC
authors.lastname: Jang
authors.affiliation: Department of Physiology, Keimyung University School of Medicine, Daegu, South Korea.
authors.forename: Seung-Soon
authors.initials: SS
authors.lastname: Im
authors.affiliation: Department of Physiology, Keimyung University School of Medicine, Daegu, South Korea.
authors.forename: Dae-Kyu
authors.initials: DK
authors.lastname: Song
authors.affiliation: Department of Physiology, Keimyung University School of Medicine, Daegu, South Korea. Electronic address: jhbae@dsmc.or.kr.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Bae
mesh_terms: D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002136:Calcium, Dietary / Q000494:pharmacology*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005944:Glucosamine / Q000494:pharmacology*; D006801:Humans; D017628:Microglia / Q000502:physiology*; D010972:Platelet Activating Factor
chemical_list: D002136:Calcium, Dietary; D010972:Platelet Activating Factor; D051546:Cyclooxygenase 2; D005944:Glucosamine; D002118:Calcium
keywords: Glucosamine; Intracellular calcium concentration; Microglia; Platelet-activating factor; Store-operated calcium channel