Morphine stimulates CCL2 production by human neurons.
BACKGROUND
Substances of abuse, such as opiates, have a variety of immunomodulatory properties that may influence both neuroinflammatory and neurodegenerative disease processes. The chemokine CCL2, which plays a pivotal role in the recruitment of inflammatory cells in the nervous system, is one of only a few chemokines produced by neurons. We hypothesized that morphine may alter expression of CCL2 by human neurons.


METHODS
Primary neuronal cell cultures and highly purified astrocyte and microglial cell cultures were prepared from human fetal brain tissue. Cell cultures were treated with morphine, and cells were examined by RNase protection assay for mRNA. Culture supernatants were assayed by ELISA for CCL2 protein. beta-funaltrexamine (beta-FNA) was used to block mu-opioid receptor (MOR)s.


RESULTS
Morphine upregulated CCL2 mRNA and protein in neuronal cultures in a concentration- and time-dependent fashion, but had no effect on CCL2 production in astrocyte or microglial cell cultures. Immunocytochemical analysis also demonstrated CCL2 production in morphine-stimulated neuronal cultures. The stimulatory effect of morphine was abrogated by beta-FNA, indicating an MOR-mediated mechanism.


CONCLUSIONS
Morphine stimulates CCL2 production by human neurons via a MOR-related mechanism. This finding suggests another mechanism whereby opiates could affect neuroinflammatory responses.
Rock
R Bryan
RB
Center for Infectious Diseases and Microbiology Translational Research and the Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA. rockx012@umn.edu
Hu
Shuxian
S
Sheng
Wen S
WS
Peterson
Phillip K
PK