THE INTERLEUKIN-1-BETA-MEDIATED REGULATION OF PROENKEPHALIN AND OPIOID RECEPTOR MESSENGER-RNA IN PRIMARY ASTROCYTE-ENRICHED CULTURES

Opioids have been found to modulate the function of the immune system by regulating the biochemical and proliferative properties of its cell ular components. The interaction of opioid and immune systems, however , is not unidirectional, but rather, bidirectional in nature. In the C NS, one cellular target of immune system activation is the astrocytes, glial cells known to synthesize proenkephalin. We have recently shown that these cells also express the messenger RNA transcripts for the o pioid receptors mu, delta and kappa, raising the question of the funct ional significance of this opioid peptide and the related receptors in the astrocytes. That is, why do astrocytes express proenkephalin and opioid receptors, and are these molecules responsive to a factor to wh ich the astrocytes could be exposed in vivo? Furthermore, do these mol ecules respond to this factor in a region-specific fashion? In the pre sent study, in order to characterize the astrocytic opioid response to an immune factor, we examined the concomitant regulation of mu, delta , kappa and proenkephalin messenger RNAs by interleukin-1 beta (1 ng/m l = 60 pM, 24 h) in primary astrocyte-enriched cultures derived from t he rat (post-natal day 1-2) cortex, striatum, cerebellum, hippocampus and hypothalamus. Interleukin-1 beta treatment was found to increase b y 55-75% the level of mu receptor messenger RNA in striatal, cerebella r and hippocampal cultures, but not in cultures derived from the corte x or hypothalamus. However, the cytokine had no effect on the level of delta receptor messenger RNA in any of the five cultures examined. In marked contrast to its stimulatory effects on mu receptor messenger R NA levels and its lack of an effect on delta receptor messenger RNA ex pression, interleukin-1 beta reduced to 10-30% of control levels the k appa receptor messenger RNA levels in all cultures. Interleukin-1 beta had no effect on the lever of proenkephalin messenger RNA in cortical , striatal, cerebellar and hypothalamic cultures, but did significantl y decrease the expression of proenkephalin messenger RNA in hippocampa l cultures to 40% of the control level. Therefore, interleukin-1 beta differentially regulated opioid receptor messenger RNA in astrocyte-en riched cultures in a manner dependent upon both the receptor type and the brain region from which the culture was derived. The cytokine also differentially regulated proenkephalin messenger RNA in a region-depe ndent fashion. These findings suggest a capacity for astrocytes to dif ferentially regulate opioid peptide and receptor messenger RNAs in res ponse to an immune factor, supporting the potential existence of a nov el immune-opioid system interaction in the CNS. (C) 1997 IBRO.