Interleukin-1 induces the expression of μ 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 μ 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 μ 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 μ opioid receptor expression at basal levels and no increase after either IL-1α or IL-1β treatment. However, simultaneous treatment with both IL-1α and IL-1β increased μ opioid receptor expression. This upregulation of μ 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.