Expression of syndecan-2 in the amoeboid microglial cells and its involvement in inflammation in the hypoxic developing brain.
The present study examined the expression of heparan sulphate proteoglycan, syndecan-2 (Sdc-2) in the corpus callosum and the amoeboid microglial cells (AMC) in the neonatal rat brain in response to hypoxia. In 1-day old Wistar rats subjected to hypoxia the mRNA and protein expression of Sdc-2 in the corpus callosum, heavily populated by AMC, was increased up to 3 days after the hypoxic exposure. Immunoexpression of Sdc-2 was localized in AMC as confirmed by double labeling using microglial marker. Primary cultures of microglial cells subjected to hypoxia showed a significant increase in Sdc-2 expression. Application of Sdc-2 to microglial cultures under hypoxia increased the release of tumor necrosis factor-alpha, interleukin-1beta, chemokine (C-C motif) ligand 2 (CCL2), and chemokine (C-X-C motif) ligand 12 (CXCL12) by the microglial cells. Additionally, Sdc-2 enhanced the production of reactive oxygen species (ROS) by microglia subjected to hypoxia. Edaravone [3-methyl-1phenyl-2-pyrazolin-5-one], an antioxidant drug, suppressed the hypoxia- and Sdc-2-induced increased production of cytokines, chemokines, and ROS. In the light of these findings, we suggest that Sdc-2 plays an important role in microglial production of inflammatory cytokines, chemokines, and ROS in hypoxic conditions. In this connection, edaravone suppressed the hypoxia- and Sdc-2-induced increased cytokine and ROS production suggesting its therapeutic potential in ameliorating neuroinflammation.
Kaur
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Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597. antkaurc@nus.edu.sg
Sivakumar
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Yip
G W
GW
Ling
E A
EA
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000983:Antipyrine / Q000031:analogs & derivatives / Q000494:pharmacology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D003337:Corpus Callosum / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D000077553:Edaravone; D005434:Flow Cytometry; D016166:Free Radical Scavengers / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D000860:Hypoxia / Q000150:complications / Q000473:pathology*; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D053669:Syndecan-2 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
D016207:Cytokines; D016166:Free Radical Scavengers; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C508247:Sdc2 protein, rat; D053669:Syndecan-2; D000077553:Edaravone; D000983:Antipyrine