Cocaine induced inflammatory response in human neuronal progenitor cells.
We have employed a genomic approach in homogenous cell culture to investigate the fundamental transcriptional responses which occur in neurons over time as a consequence of a single 30-min exposure to cocaine. Data from 24 Affymetrix microarrays, representing eight treatment groups, were analyzed by GeneChip Operating Software and then further mined by hierarchical clustering, anova, and Ingenuity Pathway Analysis software to examine known molecular pathways impacted by the observed transcriptional changes. For each time point under investigation, the data sets of genes exhibiting altered expression in treated cells compared with control were interrogated with a specific focus on differential expression of genes involved in immunomodulation and inflammation. The existing literature on the effects of cocaine in a diverse array of experimental paradigms demonstrates a significant modulation of inflammation and immune mechanisms, but these have typically been studies of chronic exposure in immune-competent cells. Our data show a time-dependent up-regulation of genes associated with pro-inflammatory and immune responses, peaking at 24 h as confirmed by all methods of analysis, suggesting a specific neuronal immunomodulatory response to acute cocaine exposure.
Crawford
Fiona C
FC
Roskamp Institute, Sarasota, Florida 34243, USA. fcrawford@rfdn.org
Wood
Marcie L
ML
Wilson
Sarah E
SE
Mathura
Venkatarajan S
VS
Hollen
Tyler R
TR
Geall
Freya
F
Kolippakkam
Deepak N
DN
Mullan
Michael J
MJ
D000704:Analysis of Variance; D016923:Cell Death / Q000187:drug effects; D016000:Cluster Analysis; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000139:chemically induced*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D046228:Microarray Analysis / Q000379:methods; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013234:Stem Cells / Q000187:drug effects*; D013997:Time Factors
D018765:Dopamine Uptake Inhibitors; D012333:RNA, Messenger; D007770:L-Lactate Dehydrogenase; D003042:Cocaine