Interleukin‐1β regulates proenkephalin gene expression in astrocytes cultured from rat cortex

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Abstract
Glial cells execute essential functions in central nervous system (CNS) development and are also believed to play important roles during gliosis in response to trauma or disease. These developmental and pathological states have also been associated with elevated expression of opioid genes. Because levels of the cytokine interleukin-1β (IL-1β) increase following CNS lesions, we examined the possible influence of IL-1β on the expression of opioid genes in astrocytes cultured from rat cortex. Proenkephalin mRNA expression was stimulated by IL-1β in a time- and concentration-dependent manner, being maximal with 5 U/ml IL-1β at 4h. Although the β-adrenergic agonist isoproternol was also active, interferon, glutamate, and carbacol were not. Unlike isoproterenol, the actions of IL-1β were not associated with a cyclic adenosine monophosphate (AMP)-dependent pathway. Interleukin-1β also regulated a proenkephalin-chloramphenicol acetyltransferase fusion gene transiently transfected into astrocytes, with a dose-response similar to that active in proenkephalin mRNA. These effects of IL-1β were region-specific, not being observed with either cerebellar or hippocampal astrocytes; however, isoproterenol was active in the latter cell populations. Proenkephalin mRNA in cortical astrocytes was stimulated following a temperature stress. These results suggest that enhanced proenkephalin gene expression in astrocytes by IL-1β may be important in neuroimmune interactions and in trauma-induced CNS injury or stress.