The μ-opioid receptor induces miR-21 expression and is ERK/PKCμ-dependent

Micro RNA-21 (miR-21) is believed to perform an important role in the transition from inflammation to resolution in the innate immune response. The biochemical basis for the induction of miR-21 remains uncertain. However, the activation of the mu-opioid receptor (MOR) induces the expression of miR-21. Our results show that human monocytes treated with mu-opioid agonists exhibit a significant increase in miR-21 expression. We found that MOR-induction of miR-21 requires the activation of the Ras-Raf-MEK-ERK signaling cascade, and to our surprise, the activation of PKC mu (PKD1). These results are significant given the role of miR-21 in the sensitivity to pain.