INTERLEUKIN-1-BETA REGULATES PROENKEPHALIN GENE-EXPRESSION IN ASTROCYTES CULTURED FROM RAT CORTEX

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-1beta (IL-1beta) increase following CNS lesions, we examined the possible influence of IL-1beta on the expression of opioid genes in astrocytes cultured from rat cortex. Proenkephalin mRNA expression was stimulated by IL-1beta in a time- and concentration-dependent manner, being maximal with 5 U/ml IL-1beta at 4 h. Although the beta-adrenergic agonist isoproterenol was also active, interferon, glutamate, and carbacol were not. Unlike isoproterenol, the actions of IL-1beta were not associated with a cyclic adenosine monophosphate (AMP)-dependent pathway. Interleukin-1beta also regulated a proenkephalin-chloramphanicol acetyltransferase fusion gene transiently transfected into astrocytes, with a dose-response similar to that active in proenkephalin mRNA. These effects of IL-1beta 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-1beta may be important in neuroimmune interactions and in trauma-induced CNS injury or stress.