Cultured human adult microglia from different donors display stable cytokine, chemokine and growth factor gene profiles but respond differently to a pro-inflammatory stimulus.
OBJECTIVE
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-alpha and IFN-gamma.


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 beta-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 Flt3 ligand. Yet, treatment with TNF-alpha and IFN-gamma led to widely different response profiles among the different cultures.


CONCLUSIONS
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.
Division Biomedical Research, TNO Prevention and Health, Leiden, The Netherlands.
Sonja
S
Meeuwsen
Malika
M
Bsibsi
Carla
C
Persoon-Deen
Rivka
R
Ravid
Johannes M
JM
van Noort
D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics*; D016207:Cytokines / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D014644:Genetic Variation / Q000276:immunology; D006133:Growth Substances / Q000235:genetics*; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008297:Male; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008875:Middle Aged; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D018925:Chemokines; D016207:Cytokines; D006133:Growth Substances; D018836:Inflammation Mediators; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma