Morphine treatment of human monocyte-derived macrophages induces differential miRNA and protein expression: impact on inflammation and oxidative stress in the central nervous system.
HIV-1-infected opiate abusers often exhibit an accelerated form of HIV-1-associated dementia and enhanced neurological dysfunction. Productive HIV-1 infection of microglia and perivascular macrophages and the resultant secretion of neurotoxic molecules by these cells contribute to this phenomenon. In order to understand the role of morphine in this process, we performed a genome-wide association study at the micro RNA (miRNA) and protein levels in human monocyte-derived macrophages (h-mdms). A total of 26 differentially expressed miRNA were identified (P < 0.01), of which hsa-miR-15b and hsa-miR-181b had the greatest increase and decrease in expression levels, respectively. Computational analysis predicted fibroblast growth factor-2 (FGF-2) as the strongest target gene for hsa-miR15b. Of note, we observed a decrease in FGF-2 protein expression in response to morphine. Both hsa-miR-15b and hsa-miR-181b have several predicted gene targets involved in inflammation and T-cell activation pathways. In this context, we observed induction of MCP-2 and IL-6 by morphine. Moreover, proteomic analysis revealed the induction of mitochondrial superoxide dismutase in response to morphine treatment. HIV-1 infection did not induce mitochondrial superoxide dismutase. Collectively, these observations demonstrate that morphine induces inflammation and oxidative stress in h-mdms thereby contributing to expansion of HIV-1 CNS reservoir expansion and disease progression. Of note, differentially expressed miRNAs (hsa-miR-15b and 181-b) may have a potential role in regulating these processes.
Dave
Rajnish S
RS
Center for Neurovirology, Department of Neuroscience, Temple University, MERB 774A, 3500 North Broad Street, Philadelphia, Pennsylvania 19140, USA. rsdave@temple.edu
Khalili
Kamel
K
D002490:Central Nervous System / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D009020:Morphine / Q000494:pharmacology*; D018384:Oxidative Stress; D011506:Proteins / Q000235:genetics*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D035683:MicroRNAs; D011506:Proteins; D009020:Morphine