Map Kinase Regulation of Ip10/Cxcl10 Chemokine Gene Expression in Microglial Cells.
From: Department of Neurosciences, Medical University of South Carolina, Charleston, 29425, USA.
Brain research
- Publish Date: May 2006
- ISSN: 0006-8993
- Volume: 1086
- Issue: 1
- Pages: 9-16
- Medium: Print
- Language: English
- Citation (JAMA): Shen Qin, Zhang Ran, Bhat Narayan R, et al. Map Kinase Regulation of Ip10/Cxcl10 Chemokine Gene Expression in Microglial Cells.. Brain Res. May 2006;1086:9-16
Abstract
Interferongamma inducible protein-10 (IP10 or CXCL10), a Th-1 affiliated chemokine, is expressed by activated glial cells and may contribute to the trafficking of immune cells in the inflamed central nervous system. This study examines the regulation of the expression of this chemokine in cultured microglial cells focusing on the roles of mitogen-activated protein (MAP) kinase cascades. Exposure of a mouse microglial cell line, BV-2, to lipopolysaccharide (LPS) and IFNgamma led to an induction of IP10 mRNA and protein as determined by RT-PCR and ELISA, respectively. This induction was suppressed by pharmacological inhibitors of p38 MAPK (i.e., SB203580) and c-Jun N-terminal kinase (JNK, SP600125), suggesting the involvement of the two kinases in IP10 expression. LPS also induced the activity of an IP10 promoter reporter (luciferase) construct transfected into BV-2 cells in a MAP kinase- and NFkappaB-dependent manner. The use of deletion constructs revealed that the kinase-targeted sequences were within the region between -533 bp and -332 bp upstream of the transcriptional start site. Co-transfection of IP10 luciferase with the active forms of the upstream kinases in the MAP kinase cascades, i.e., MAPK kinase-3 (MKK3), MKK6 (the immediately upstream activators of p38 kinase) and a MAP3K, i.e., TGFbeta-activated kinase-1 (TAK1), produced a marked stimulation of the promoter activity. The results of this study indicate that the MAP kinase cascades prominently regulate IP10 gene expression in microglial cells.
Mesh Headings (Keywords): Analysis of Variance, Animals, Anthracenes, Blotting, Western, Cell Line, Chemokine CXCL10, Chemokines, CXC, Drug Interactions, Enzyme Inhibitors, Enzyme-Linked Immunosorbent Assay, Gene Expression, Gene Expression Regulation, Imidazoles, Interferon Type II, Lipopolysaccharides, Luciferases, Mice, Microglia, Mitogen-Activated Protein Kinases, Pyridines, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, Transfection
Check for Full Text / PubMed Unique Identifier (PMID): 16635481
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