Regulation of tumour necrosis factor and interleukin-6 gene transcription by beta2-adrenoceptor in the rat astrocytes.
The present study was designed to clarify the role of beta2-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 beta2-adrenoceptor antagonist but not in the presence of a beta1-adrenoceptor antagonist. TNF and IL-6 mRNA and protein levels in the astrocytes were depressed by beta2-adrenoceptor activation which corresponded to changes in TNF and IL-6 promoter activity. These studies demonstrated that isoproterenol, via beta2-adrenoceptors, suppressed LPS-induced TNF and IL-6 promoter activities, mRNA accumulations, and protein levels in the astrocytes. Beta2-adrenoceptor activation may be an important mechanism for regulating TNF and IL-6 expression in brain diseases.
Nakamura
A
A
Department of Paediatrics, Teikyo University School of Medicine, Tokyo, Japan. akio@fuji.med.teikyo-u.ac.jp
Johns
E J
EJ
Imaizumi
A
A
Abe
T
T
Kohsaka
T
T
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D001262:Atenolol / Q000494:pharmacology; D002478:Cells, Cultured; D015850:Interleukin-6 / Q000235:genetics*; D007545:Isoproterenol / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats / Q000196:embryology; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D015850:Interleukin-6; D011412:Propanolamines; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D014409:Tumor Necrosis Factor-alpha; C026777:ICI 118551; D001262:Atenolol; D007545:Isoproterenol