title: NG2, a member of chondroitin sulfate proteoglycans family mediates the inflammatory response of activated microglia.
abstract: Activation of microglial cells, the resident immune cells of the CNS causes neurotoxicity through the release of a wide array of inflammatory mediators including proinflammatory cytokines, chemokines and reactive oxygen species. In this study, we have investigated the expression of NG2 (also known as CSPG4), one of the members of transmembrane chondroitin sulfate proteoglycans family, in microglial cells and its role on inflammatory reaction of microglia by analyzing the expression of the proinflammation cytokines (interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha)), chemokines (stromal cell-derived factor-1alpha and monocyte chemotactic protein-1) and inducible nitric oxide synthase (iNOS). NG2 expression was not detectable in microglial cells expressing OX-42 in the brains of 1-day old postnatal rat pups and adult rats; it was, however, induced in activated microglial cells in pups and adult rats injected with lipopolysaccharide (LPS). In vitro analysis further confirmed that LPS induced the expression of NG2 in primary microglial cells and this was inhibited by dexamethasone. It has been well demonstrated that LPS induces the expression of iNOS and proinflammatory cytokines in microglia. However in this study, LPS did not induce the mRNA expression of iNOS and cytokines including IL-1beta, and TNF-alpha in microglial cells transfected with CSPG4 siRNA. On the contrary, mRNA expression of chemokines such as monocyte chemoattractant protein-1 (MCP-1) and stromal cell-derived factor-1alpha (SDF-1alpha) was significantly increased in LPS-activated microglial cells after CSPG4 siRNA transfection in comparison with the control. The above results indicate that NG2 mediates the induction of iNOS and inflammatory cytokine expression, but not the chemokine expression in activated microglia.
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Q
authors.initials: Q
authors.lastname: Gao
authors.forename: J
authors.initials: J
authors.lastname: Lu
authors.forename: Y
authors.initials: Y
authors.lastname: Huo
authors.forename: N
authors.initials: N
authors.lastname: Baby
authors.forename: E A
authors.initials: EA
authors.lastname: Ling
authors.forename: S T
authors.initials: ST
authors.lastname: Dheen
mesh_terms: D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000941:Antigens / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000276:immunology* / Q000502:physiology*; D018932:Chemokine CCL2 / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D017628:Microglia / Q000187:drug effects / Q000276:immunology* / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000893:Anti-Inflammatory Agents; D000941:Antigens; D018932:Chemokine CCL2; D054377:Chemokine CXCL12; D003907:Dexamethasone; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D052247:Nitric Oxide Synthase Type II; D011509:Proteoglycans; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D000099216:Chondroitin Sulfate Proteoglycan 4; C491766:Ccl2 protein, rat