Cultured Human Adult Microglia from Different Donors Display Stable Cytokine, Chemokine and Growth Factor Gene Profiles but Respond Differently to a Pro-Inflammatory Stimulus

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 Flt3 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.