INTERLEUKIN-1 INDUCES THE EXPRESSION OF MU-OPIOID RECEPTORS IN ENDOTHELIAL-CELLS

Immunocytokines, such as interleukin-1 (IL-1), have been shown to be i nvolved in the activation and/or induction of a variety of transcripti on factors which may modulate the expression of genes possessing DNA b inding sites on which these transcription factors act. The promoter DN A sequence of the mu opioid receptor gene contains IL-1 response eleme nts such as NF-IL6, and, therefore, the receptor gene may be responsiv e to IL-1. To investigate the effect of IL-1 on the opioid receptor ge ne, the in vitro expression of mu opioid receptor mRNA in neural micro vascular endothelial cells (NMVEC) was determined before and after IL- 1 treatment. PCR analysis revealed that there was virtually no mu opio id receptor expression at basal levels and no increase after either IL -1 alpha or IL-1 beta treatment. However, simultaneous treatment with both IL-1 alpha and IL-1 beta increased mu opioid receptor expression. This upregulation of mu opioid receptor expression provides direct ev idence of a relationship between opioid and cytokine actions, and sugg ests that opioid-dependent pathways may be modulated in the disease st ate. (C) 1998 Elsevier Science B.V.