Cultured human adult microglia from different donors display stable cytokine, chemokine and growth factor gene profiles but respond differently to a pro-inflammatory stimulus
article
Objectives: Brain microglia are highly responsive cells in the central nervous system that exert key functions in host defense as well as in neuroprotection and regeneration. In this study the gene expression profiles for 268 cytokines, chemokines, growth factors and their receptors were examined in cultures of purified human adult microglia, using cDNA array profiling. Methods: Microglia from 9 different donors were compared, also following challenge of such microglia with the pro-inflammatory cytokines TNF-α and IFN-γ. Results: A stable pattern was observed of genes abundantly expressed in the different cultures under standard conditions. Genes abundantly expressed in all microglia cultures include CCL2 (MCP-1), thymosin β-10, migration-inhibitory factor-related protein 8 (MRP8), MRP14, corticotropin-releasing factor receptor 1 and endothelin 2. Abundant gene products novel to microglia were neuromodulin (GAP43) and FltS ligand. Yet, treatment with TNF-α and IFN-γ led to widely different response profiles among the different cultures. Conclusion: These data show a surprising level of heterogeneity among human adult microglia cultures in their response to a pro-inflammatory stimulus despite the standardized methodology to examine this response. Copyright © 2005 S. Karger AG. Chemicals / CAS: Flt3 ligand, 171404-15-2; gamma interferon, 82115-62-6; migration inhibition factor, 125523-65-1; thymosin beta10, 87397-91-9; Chemokines; Cytokines; Growth Substances; Inflammation Mediators; Interferon Type II, 82115-62-6; RNA, Messenger; Tumor Necrosis Factor-alpha
Topics
Growth factorMicrogliacomplementary DNAcorticotropin releasing factor receptor 1endothelin 2Flt3 ligandgamma interferonmigration inhibition factorneuromodulinthymosin beta10tumor necrosis factor alphacell culturecomparative studycontrolled studyDNA microarraygene expressionhumanhuman cellmicrogliastimulus responseAgedAged, 80 and overCells, CulturedChemokinesCytokinesFemaleGene Expression ProfilingGene Expression RegulationGrowth SubstancesHumansInflammation MediatorsInterferon Type IIMaleMicrogliaMiddle AgedNeuroimmunomodulationOligonucleotide Array Sequence AnalysisRNA, MessengerTumor Necrosis Factor-alphaUp-RegulationVariation (Genetics)
TNO Identifier
238600
ISSN
10217401
Source
NeuroImmunoModulation, 12(4), pp. 235-245.
Pages
235-245
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