Effect of beta(2)-adrenoceptor activation and angiotensin II on tumour necrosis factor and interleukin 6 gene transcription in the rat renal residentmacrophage cells

This study aimed to examine whether lipopolysaccharide (LPS)-induced increa se in tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) gen e transcription was regulated by beta-adrenoceptor activation and whether T NF-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 b y the high concentration (10 M-5) of isoproterenol, The addition of beta(2) -adrenoceptor antagonist (ICI118,551), but not a beta(1)-adrenoceptor antag onist (atenolol), blocked the inhibitory effect of isoproterenol. By contra st, 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 c ells was altered with beta(2)-adrenoceptor agonists (terbutaline, formotero l) 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 throug h the regulation of TNF-alpha and IL-6 gene transcription by the renal resi dent macrophage cells. (C) 1999 Academic Press.