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Opioid‐immune crosstalk: role of microRNA regulation following opioid and cytokine treatment in normal human astrocytes
Author(s) -
Stevens Craig W.,
Castoro Ryan J.,
Davis Randall L.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1175.4
Subject(s) - crosstalk , immune system , microrna , signal transduction , microbiology and biotechnology , cytokine , opioid , mediator , innate immune system , biology , receptor , immunology , gene , biochemistry , physics , optics
There is great interest in the interaction of opioid and cytokine ligands and their respective signaling molecules in neural and immune cells. One avenue of research that is largely unexplored focuses on the role of microMNA (miRNA) as a mediator of opioid‐immune crosstalk. This project focused on two miRNA species: miR‐146a and miR‐let7a. The role miRNA‐146a was established as important for the regulation of NFκB pathways in peripheral immune cells as its expression is increased with pro‐inflammatory cytokines and miR‐146a then decreases the expression of key positive protein partners in the NFκB pathway, such as IRAK1 and TRAF6. The role of miR‐let7a is established in the regulation of the mu opioid receptor (MOR) and its increased expression downregulated MOR mRNA at by post‐transcriptional mechanisms. Recent preliminary data from our laboratory shows that unstimulated normal human astrocytes (NHA) express low levels of and that MOR is increased by treatment with the cytokine, interleukin‐1β (IL‐1β). At the same time, IL‐1β treatment increased the expression of miR‐146a, a key miRNA species recognized to play a role in dampening innate immune signaling pathways. Confirmation of the regulatory role of miR‐146a in signaling pathways in NHA cells was done by Western immunoblots of the NFκB protein partners, IRAK1 and TRAF6. Treatment of NHA cells with IL‐1β decreased the protein expression of IRAK1 at 12 and 24h. Treatment of NHA cells with IL‐1β also decreased the protein expression of TRAF6 at 24h. The miRNA, miR‐let7a is also expressed in NHA cells and is regulated by morphine and IL‐1β treatment of NHA cells. These studies suggest that miRNA may play a role in the opioid‐immune crosstalk observed in numerous peripheral immune cell studies and centers the attention on innate immune cells in the brain, namely the astrocytes. Supported in part by Oklahoma Center for Advancement of Science and Technology (OCAST) contract HR10–31 to CWS.