Interleukin-1 induces the expression of mu opioid receptors in endothelial cells.

Immunocytokines, such as interleukin-1 (IL-1), have been shown to be involved in the activation and/or induction of a variety of transcription factors which may modulate the expression of genes possessing DNA binding sites on which these transcription factors act. The promoter DNA sequence of the mu opioid receptor gene contains IL-1 response elements such as NF-IL6, and, therefore, the receptor gene may be responsive to IL-1. To investigate the effect of IL-1 on the opioid receptor gene, the in vitro expression of mu opioid receptor mRNA in neural microvascular endothelial cells (NMVEC) was determined before and after IL-1 treatment. PCR analysis revealed that there was virtually no mu opioid receptor expression at basal levels and no increase after either IL-1alpha or IL-1beta treatment. However, simultaneous treatment with both IL-1alpha and IL-1beta increased mu opioid receptor expression. This upregulation of mu opioid receptor expression provides direct evidence of a relationship between opioid and cytokine actions, and suggests that opioid-dependent pathways may be modulated in the disease state.