Regulation of tumour necrosis factor and interleukin-6 gene transcription by β2-adrenoceptor in the rat astrocytes

Abstract

The present study was designed to clarify the role of β 2-adrenoceptors in modulating the level of TNF and IL-6 gene transcription and their respective mRNA accumulations. Astrocytes were transfected with the 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 inhibitory effect on the TNF and IL-6 promoter activity induced by LPS. The inhibitory effect was blocked in the presence of a β 2-adrenoceptor antagonist but not in the presence of a β 1-adrenoceptor antagonist. TNF and IL-6 mRNA and protein levels in the astrocytes were depressed by β 2-adrenoceptor activation which corresponded to changes in TNF and IL-6 promoter activity. These studies demonstrated that isoproterenol, via β 2-adrenoceptors, suppressed LPS-induced TNF and IL-6 promoter activities, mRNA accumulations, and protein levels in the astrocytes. β 2-adrenoceptor activation may be an important mechanism for regulating TNF and IL-6 expression in brain diseases.