REGULATION OF TUMOR-NECROSIS-FACTOR AND INTERLEUKIN-6 GENE-TRANSCRIPTION BY BETA(2)-ADRENOCEPTOR IN THE RAT ASTROCYTES

The present study was designed to clarify the role of beta(2)-adrenoce ptors in modulating the level of TNF and IL-6 gene transcription and t heir respective mRNA accumulations. Astrocytes were transfected with t he 5'-flanking region of the TNF and IL-6 genes linked to a luciferase coding sequence as a reporter. The addition of isoproterenol had an i nhibitory effect on the TI IF and IL-6 promoter activity induced by LP S. The inhibitory effect was blocked in the presence of a beta(2)-adre noceptor antagonist but not in the presence of a beta(1)-adrenoceptor antagonist. TNF and IL-6 mRNA and protein levels in the astrocytes wer e depressed by beta(2)-adrenoceptor activation which corresponded to c hanges in TNF and IL-6 promoter activity. These studies demonstrated t hat isoproterenol, via beta(2)-adrenoceptors, suppressed LPS-induced T NF and IL-6 promoter activities, mRNA accumulations, and protein level s in the astrocytes. beta(2)-adrenoceptor activation may be an importa nt mechanism for regulating TNF and IL-6 expression in brain diseases. (C) 1998 Elsevier Science B.V. All rights reserved.