PubMed:19285061 JSONTXT

{"project":"bionlp-st-pc-2013-training","denotations":[{"id":"T1","span":{"begin":0,"end":10},"obj":"Gene_or_gene_product"},{"id":"T2","span":{"begin":24,"end":37},"obj":"Gene_or_gene_product"},{"id":"T3","span":{"begin":46,"end":51},"obj":"Gene_or_gene_product"},{"id":"T4","span":{"begin":53,"end":57},"obj":"Gene_or_gene_product"},{"id":"T5","span":{"begin":58,"end":61},"obj":"Gene_or_gene_product"},{"id":"T6","span":{"begin":63,"end":66},"obj":"Gene_or_gene_product"},{"id":"T7","span":{"begin":72,"end":81},"obj":"Complex"},{"id":"T8","span":{"begin":114,"end":143},"obj":"Gene_or_gene_product"},{"id":"T9","span":{"begin":145,"end":150},"obj":"Gene_or_gene_product"},{"id":"T10","span":{"begin":167,"end":173},"obj":"Gene_or_gene_product"},{"id":"T11","span":{"begin":183,"end":216},"obj":"Gene_or_gene_product"},{"id":"T12","span":{"begin":218,"end":223},"obj":"Gene_or_gene_product"},{"id":"T13","span":{"begin":290,"end":295},"obj":"Gene_or_gene_product"},{"id":"T14","span":{"begin":296,"end":301},"obj":"Gene_or_gene_product"},{"id":"T15","span":{"begin":364,"end":369},"obj":"Gene_or_gene_product"},{"id":"T16","span":{"begin":535,"end":545},"obj":"Gene_or_gene_product"},{"id":"T17","span":{"begin":546,"end":551},"obj":"Gene_or_gene_product"},{"id":"T18","span":{"begin":634,"end":644},"obj":"Gene_or_gene_product"},{"id":"T19","span":{"begin":654,"end":658},"obj":"Gene_or_gene_product"},{"id":"T20","span":{"begin":783,"end":787},"obj":"Gene_or_gene_product"},{"id":"T21","span":{"begin":813,"end":823},"obj":"Gene_or_gene_product"},{"id":"T22","span":{"begin":838,"end":848},"obj":"Gene_or_gene_product"},{"id":"T23","span":{"begin":859,"end":863},"obj":"Gene_or_gene_product"},{"id":"T24","span":{"begin":941,"end":944},"obj":"Gene_or_gene_product"},{"id":"T25","span":{"begin":946,"end":975},"obj":"Gene_or_gene_product"},{"id":"T26","span":{"begin":977,"end":981},"obj":"Gene_or_gene_product"},{"id":"T27","span":{"begin":984,"end":993},"obj":"Complex"},{"id":"T28","span":{"begin":1010,"end":1017},"obj":"Gene_or_gene_product"},{"id":"T29","span":{"begin":1068,"end":1078},"obj":"Gene_or_gene_product"},{"id":"T30","span":{"begin":1094,"end":1097},"obj":"Gene_or_gene_product"},{"id":"T31","span":{"begin":1102,"end":1108},"obj":"Gene_or_gene_product"},{"id":"T32","span":{"begin":1139,"end":1149},"obj":"Gene_or_gene_product"},{"id":"T33","span":{"begin":1175,"end":1195},"obj":"Gene_or_gene_product"},{"id":"T34","span":{"begin":1196,"end":1200},"obj":"Gene_or_gene_product"},{"id":"T35","span":{"begin":1202,"end":1211},"obj":"Gene_or_gene_product"},{"id":"T36","span":{"begin":1212,"end":1216},"obj":"Gene_or_gene_product"},{"id":"T37","span":{"begin":1235,"end":1247},"obj":"Gene_or_gene_product"},{"id":"T38","span":{"begin":1265,"end":1277},"obj":"Gene_or_gene_product"},{"id":"T39","span":{"begin":1291,"end":1294},"obj":"Gene_or_gene_product"},{"id":"T40","span":{"begin":1314,"end":1322},"obj":"Simple_chemical"},{"id":"T41","span":{"begin":1341,"end":1344},"obj":"Gene_or_gene_product"},{"id":"T42","span":{"begin":1349,"end":1352},"obj":"Gene_or_gene_product"},{"id":"T43","span":{"begin":1358,"end":1365},"obj":"Cellular_component"},{"id":"T44","span":{"begin":1369,"end":1376},"obj":"Cellular_component"},{"id":"T45","span":{"begin":1381,"end":1387},"obj":"Complex"},{"id":"T46","span":{"begin":1419,"end":1429},"obj":"Gene_or_gene_product"},{"id":"T47","span":{"begin":1451,"end":1457},"obj":"Complex"},{"id":"T48","span":{"begin":1518,"end":1521},"obj":"Gene_or_gene_product"},{"id":"T49","span":{"begin":1526,"end":1529},"obj":"Gene_or_gene_product"},{"id":"T50","span":{"begin":1536,"end":1540},"obj":"Gene_or_gene_product"},{"id":"T51","span":{"begin":1554,"end":1563},"obj":"Gene_or_gene_product"},{"id":"T52","span":{"begin":1564,"end":1568},"obj":"Gene_or_gene_product"},{"id":"T53","span":{"begin":1600,"end":1603},"obj":"Gene_or_gene_product"},{"id":"T54","span":{"begin":1608,"end":1611},"obj":"Gene_or_gene_product"},{"id":"T55","span":{"begin":1619,"end":1628},"obj":"Complex"},{"id":"T56","span":{"begin":1662,"end":1666},"obj":"Gene_or_gene_product"},{"id":"T57","span":{"begin":1671,"end":1674},"obj":"Gene_or_gene_product"},{"id":"T58","span":{"begin":1731,"end":1741},"obj":"Gene_or_gene_product"},{"id":"T59","span":{"begin":1746,"end":1750},"obj":"Gene_or_gene_product"},{"id":"T60","span":{"begin":1803,"end":1813},"obj":"Gene_or_gene_product"}],"text":"SDF-1alpha up-regulates interleukin-6 through CXCR4, PI3K/Akt, ERK, and NF-kappaB-dependent pathway in microglia.\nStromal cell-derived factor-1 (SDF-1), also known as CXCL12, and its receptor CXC chemokine receptor 4 (CXCR4) express in various kinds of cells in central nervous system. The SDF-1/CXCR4 signaling pathway is regulated by diverse biological effects. SDF-1 is up-regulated in the ischemic penumbra following stroke and has been known to be associated with the homing of bone marrow cells to injury. However, the effect of SDF-1alpha/CXCR4 on cytokine production in microglia is mostly unknown. Here, we demonstrated that SDF-1alpha enhanced IL-6 production in both primary cultured microglia and BV-2 microglia. We further investigated the signaling pathway involved in IL-6 production stimulated by SDF-1alpha in microglia. SDF-1alpha increased IL-6 production in both protein and mRNA levels. These effects were attenuated by ERK, phosphatidylinositol 3-kinase (PI3K), NF-kappaB inhibitors, and IkappaB protease inhibitor. Stimulation of microglia with SDF-1alpha also increased Akt and ERK1/2 phosphorylation. In addition, SDF-1alpha treatment also increased IkappaB kinase alpha/beta (IKK alpha/beta) phosphorylation, IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation at Ser(276), translocation of p65 and p50 from cytosol to nucleus and kappaB-luciferase activity. Moreover, SDF-1alpha-mediated increase of kappaB-luciferase activity was inhibited by pre-transfection of DN-p85, DN-Akt or DN-ERK2. Increase of IKK alpha/beta phosphorylation and binding of p65 and p50 to the NF-kappaB element were both antagonized by PI3K and ERK inhibitors. Our results demonstrate a mechanism linking SDF-1alpha and IL-6, and provide additional support for the notion that SDF-1alpha plays a regulatory role in microglia activation."}