Article (Scientific journals)
Microarray analysis of tumor necrosis factor alpha induced gene expression in U373 human glioblastoma cells.
Schwamborn, Jens Christian; Lindecke, Antje; Elvers, Margitta et al.
2003In BMC Genomics, 4 (1), p. 46
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Keywords :
Cell Line, Tumor/drug effects/metabolism; Chemokine CCL2/genetics/metabolism; Cluster Analysis; Enzyme-Linked Immunosorbent Assay; Gene Expression Profiling; Gene Expression Regulation, Neoplastic/drug effects; Glioblastoma/genetics/metabolism/pathology; Humans; Oligonucleotide Array Sequence Analysis/methods; Time Factors; Tumor Necrosis Factor-alpha/pharmacology
Abstract :
[en] BACKGROUND: Tumor necrosis factor alpha (TNF) is able to induce a variety of biological responses in the nervous system including inflammation and neuroprotection. Human astrocytoma cells U373 have been widely used as a model for inflammatory cytokine actions in the nervous system. Here we used cDNA microarrays to analyze the time course of the transcriptional response from 1 h up to 12 h post TNF treatment in comparison to untreated U373 cells. TNF activated strongly the NF-kappaB transcriptional pathway and is linked to other pathways via the NF-kappaB target genes JUNB and IRF-1. Part of the TNF-induced gene expression could be inhibited by pharmacological inhibition of NF-kappaB with pyrrolidine-dithiocarbamate (PDTC). NF-kappaB comprises a family of transcription factors which are involved in the inducible expression of genes regulating neuronal survival, inflammatory response, cancer and innate immunity. RESULTS: In this study we show that numerous genes responded to TNF (> 880 from 7500 tested) with a more than two-fold induction rate. Several novel TNF-responsive genes (about 60% of the genes regulated by a factor > or = 3) were detected. A comparison of our TNF-induced gene expression profiles of U373, with profiles from 3T3 and Hela cells revealed a striking cell-type specificity. SCYA2 (MCP-1, CCL2, MCAF) was induced in U373 cells in a sustained manner and at the highest level of all analyzed genes. MCP-1 protein expression, as monitored with immunofluorescence and ELISA, correlated exactly with microarray data. Based on these data and on evidence from literature we suggest a model for the potential neurodegenerative effect of NF-kappaB in astroglia: Activation of NF-kappaB via TNF results in a strongly increased production of MCP-1. This leads to a exacerbation of neurodegeneration in stoke or Multiple Sclerosis, presumably via infiltration of macrophages. CONCLUSIONS: The vast majority of genes regulated more than 3-fold were previously not linked to tumor necrosis factor alpha as a search in published literature revealed. Striking co-regulation for several functional groups such as proteasome and ribosomal proteins were detected.
Disciplines :
Genetics & genetic processes
Author, co-author :
Schwamborn, Jens Christian ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Lindecke, Antje
Elvers, Margitta
Horejschi, Volker
Kerick, Martin
Rafigh, Mehran
Pfeiffer, Julia
Prullage, Maria
Kaltschmidt, Barbara
Kaltschmidt, Christian
Language :
English
Title :
Microarray analysis of tumor necrosis factor alpha induced gene expression in U373 human glioblastoma cells.
Publication date :
2003
Journal title :
BMC Genomics
ISSN :
1471-2164
Publisher :
BioMed Central, United Kingdom
Volume :
4
Issue :
1
Pages :
46
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBilu :
since 21 June 2013

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