Effect of beta(2)-adrenoceptor activation and angiotensin II on tumour necrosis factor and interleukin 6 gene transcription in the rat renal resident macrophage cells.
This study aimed to examine whether lipopolysaccharide (LPS)-induced increase in tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) gene transcription was regulated by beta-adrenoceptor activation and whether TNF-alpha and IL-6 gene transcription was regulated by angiotensin II in rat renal resident macrophage cells. The cells were transfected with a fusion gene with the 5'-flanking region of rat TNF-alpha or IL-6 genes linked to a luciferase coding sequence as a reporter. The stimulatory effect of LPS on TNF-alpha transcription was suppressed by isoproterenol (10(-8)-10(-5)M) in a dose-dependent manner, whereas IL-6 transcription was only decreased by the high concentration (10(-5)M) of isoproterenol. The addition of beta(2)-adrenoceptor antagonist (ICI118,551), but not a beta(1)-adrenoceptor antagonist (atenolol), blocked the inhibitory effect of isoproterenol. By contrast, angiotensin II (10(-8)-10(-5)M) enhanced IL-6 gene transcription in the cells in a dose-dependent manner which was inhibited by type 1 angiotensin II receptor antagonist (CV11,974). TNF-alpha and IL-6 secretion from the cells was altered with beta(2)-adrenoceptor agonists (terbutaline, formoterol) and angiotensin II corresponding to changes of TNF-alpha and IL-6 gene transcription. Angiotensin II had no effect on TNF-alpha secretion and gene transcription. These findings suggested that beta(2)-adrenoceptor agonist and angiotensin II potentially could influence renal immune function through the regulation of TNF-alpha and IL-6 gene transcription by the renal resident macrophage cells.
Nakamura
A
A
Department of Paediatrics, Teikyo University School of Medicine, Tokyo, 173, Japan. akio@fuji.med.teikyo-u.ac.jp
Johns
E J
EJ
Imaizumi
A
A
Yanagawa
Y
Y
Kohsaka
T
T
D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D017930:Genes, Reporter / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000166:cytology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D015850:Interleukin-6; D008070:Lipopolysaccharides; D018343:Receptors, Adrenergic, beta-2; D013777:Tetrazoles; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; C081643:candesartan