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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2006-9-25
pubmed:abstractText
In the present study we sought to examine cell-cell interactions by investigating the effects of factors released by stimulated microglia on inducible nitric oxide (NO) synthase (iNOS) induction in astrocytoma cells. After examining the temporal profiles of proinflammatory molecules induced by lipopolysaccharide (LPS) stimulation in BV2 microglial cells, iNOS and IL-1beta were observed to be the first immediate-response molecules. Removal of LPS after 3 hr stimulation abrogated NO release, whereas a full induction of IL-1beta was retained in BV2 cells. We observed consistently that conditioned medium (CM) from activated microglia resulted in the induction of iNOS in C6 cells, and IL-1beta was shown to be a key regulator of iNOS induction. An IL-1beta-neutralizing antibody diminished NO induction. Incubation with recombinant IL-1beta stimulated NO release to a lesser extent compared to microglial CM; co-treatment of LPS and IL-1beta had a potent, synergistic effect on NO release from C6 cells. Transient transfection with MEK kinase 1 (MEKK1) or nuclear factor-kappa B (NF-kappaB) expression plasmids induced iNOS, and IL-1beta further enhanced the MEKK1 response. Furthermore, IL-1beta-mediated NO release from C6 cells was significantly suppressed by inhibition of p38 mitogen activated protein kinase (MAPK) or NF-kappaB by specific chemical inhibitors. Both IL-1beta and MEKK1 stimulated p38 and JNK MAPKs, as well as the NF-kappaB pathway, to induce iNOS in C6 cells. Microglia may represent an anti-tumor response in the central nervous system, which is potentiated by the local secretion of immunomodulatory factors that in turn affects astrocytoma (glioma) cells. A better understanding of microglia-glioma or microglia-astrocyte interactions will help in the design of novel immune-based therapies for brain tumors or neuronal diseases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0360-4012
pubmed:author
pubmed:copyrightInfo
Copyright 2006 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:volume
84
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1037-46
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16881054-Analysis of Variance, pubmed-meshheading:16881054-Animals, pubmed-meshheading:16881054-Animals, Newborn, pubmed-meshheading:16881054-Astrocytoma, pubmed-meshheading:16881054-Blotting, Western, pubmed-meshheading:16881054-Cells, Cultured, pubmed-meshheading:16881054-Electrophoretic Mobility Shift Assay, pubmed-meshheading:16881054-Enzyme Activation, pubmed-meshheading:16881054-Enzyme Inhibitors, pubmed-meshheading:16881054-Interleukin-1beta, pubmed-meshheading:16881054-Lipopolysaccharides, pubmed-meshheading:16881054-Mice, pubmed-meshheading:16881054-Microglia, pubmed-meshheading:16881054-NF-kappa B, pubmed-meshheading:16881054-Nitric Oxide, pubmed-meshheading:16881054-Nitric Oxide Synthase Type II, pubmed-meshheading:16881054-RNA, Messenger, pubmed-meshheading:16881054-Rats, pubmed-meshheading:16881054-Rats, Sprague-Dawley, pubmed-meshheading:16881054-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:16881054-Signal Transduction, pubmed-meshheading:16881054-Transfection, pubmed-meshheading:16881054-p38 Mitogen-Activated Protein Kinases
pubmed:year
2006
pubmed:articleTitle
IL-1beta, an immediate early protein secreted by activated microglia, induces iNOS/NO in C6 astrocytoma cells through p38 MAPK and NF-kappaB pathways.
pubmed:affiliation
Department of Physiology and Biophysics, and Center for Advanced Medical Education by BK21 Project, Inha University, College of Medicine, Incheon, Korea.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't