Microarray analysis of tumor necrosis factor alpha induced gene expression in U373 human glioblastoma cells
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2003 |
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| Erschienen: |
2003 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:4 |
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| Enthalten in: |
BMC genomics - 4(2003), 1 vom: 25. Nov., Seite 46 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Schwamborn, Jens [VerfasserIn] |
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| Themen: |
Chemokine CCL2 |
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| Anmerkungen: |
Date Completed 15.06.2004 Date Revised 13.11.2018 published: Electronic Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM143575929 |
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| 100 | 1 | |a Schwamborn, Jens |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Microarray analysis of tumor necrosis factor alpha induced gene expression in U373 human glioblastoma cells |
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| 500 | |a Date Revised 13.11.2018 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Chemokine CCL2 |2 NLM | |
| 650 | 7 | |a Tumor Necrosis Factor-alpha |2 NLM | |
| 700 | 1 | |a Lindecke, Antje |e verfasserin |4 aut | |
| 700 | 1 | |a Elvers, Margitta |e verfasserin |4 aut | |
| 700 | 1 | |a Horejschi, Volker |e verfasserin |4 aut | |
| 700 | 1 | |a Kerick, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Rafigh, Mehran |e verfasserin |4 aut | |
| 700 | 1 | |a Pfeiffer, Julia |e verfasserin |4 aut | |
| 700 | 1 | |a Prüllage, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Kaltschmidt, Barbara |e verfasserin |4 aut | |
| 700 | 1 | |a Kaltschmidt, Christian |e verfasserin |4 aut | |
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