PMID- 15579277 OWN - NLM STAT- MEDLINE DCOM- 20050222 LR - 20071114 IS - 0165-5728 (Print) IS - 0165-5728 (Linking) VI - 157 IP - 1-2 DP - 2004 Dec TI - Microarray analysis of activated mixed glial (microglia) and monocyte-derived macrophage gene expression. PG - 27-38 AB - Since macrophage activation can now be studied at a global level using modern microarray and proteomic analyses, discovery of novel macrophage activation genes is inevitable and important for understanding HIV-associated dementia (HAD). We isolated two different types of primary human macrophages: microglia and monocyte-derived macrophages (MDM) from brain tissue and whole blood, respectively. The microarray analysis of differentially regulated macrophage activation genes reported here supports our previous assertions that the mixed glia (MIX) cultured in starvation conditions (DMEM alone) are a non-activated, or "quiescent", tissue culture model for studying macrophage activation in the brain. Transcript levels from these quiescent cultures provided a background level of gene expression and allowed for the identification of upregulated macrophage activation genes in the MIX brain cultures upon treatment with an array of soluble activation factors: serum components, cytokines, and growth factors. We found that 914 genes in the MIX cultures and 734 genes in the MDM cultures had a greater than twofold increase in expression. We discovered 180 genes with expression that was increased more than twofold in both culture types. Microarray-specific statistical analyses were performed to complement fold change analysis: significance analysis of microarrays (SAM) and Partek Pro. In the MIX cultures, we detected over a 100-fold increase in IL-1beta and TIMP1 transcription; Caspase 9, S100A8 and 9, MMP12, IL-8, monocyte chemotactic protein 1 (MCP1), MRC-1, and IL-6 were also upregulated. Activation of starved MDM cultures resulted in fewer upregulated genes compared to MIX cultures. Genes upregulated in both MIX and MDM included CCL2 (MCP1), CCL7, CXCL5, TNFSF14, kinases, and phosphatases. These microarray data may provide leads for identifying previously unknown neurotoxins, disease biomarkers, and pathways responsible for the neuronal apoptosis observed in HAD and for the eventual identification of therapeutic targets and treatments. FAU - Albright, Andrew V AU - Albright AV AD - Department of Neurology, University of Pennsylvania, 255 Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104-6146, USA. albright@mail.med.upenn.edu FAU - Gonzalez-Scarano, Francisco AU - Gonzalez-Scarano F LA - eng GR - NS-27405/NS/NINDS NIH HHS/United States GR - NS36573/NS/NINDS NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - Netherlands TA - J Neuroimmunol JT - Journal of neuroimmunology JID - 8109498 RN - 0 (Culture Media, Serum-Free) RN - 0 (Cytokines) RN - 0 (Growth Substances) SB - IM MH - Analysis of Variance MH - Brain/*cytology MH - Cells, Cultured MH - Culture Media, Serum-Free/pharmacology MH - Cytokines/pharmacology MH - *Gene Expression Profiling MH - Growth Substances/pharmacology MH - Humans MH - Macrophage Activation/drug effects/*genetics MH - Macrophages/drug effects/*metabolism MH - Microarray Analysis/methods MH - Neuroglia/*metabolism EDAT- 2004/12/08 09:00 MHDA- 2005/02/23 09:00 CRDT- 2004/12/08 09:00 PHST- 2004/12/08 09:00 [pubmed] PHST- 2005/02/23 09:00 [medline] PHST- 2004/12/08 09:00 [entrez] AID - S0165-5728(04)00330-3 [pii] AID - 10.1016/j.jneuroim.2004.09.007 [doi] PST - ppublish SO - J Neuroimmunol. 2004 Dec;157(1-2):27-38. doi: 10.1016/j.jneuroim.2004.09.007.