We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Modulation of interleukin-6 by β<sub>2</sub>-adrenoceptor in endotoxin-stimulated renal macrophage cells.
- Authors
Nakamura, Akio; Johns, Edward J.; Imaizumi, Akira; Yanagawa, Yukishige; Kohsaka, Takao
- Abstract
Modulation of interleukin-6 by β2-adrenoceptor in endotoxin-stimulated renal macrophage cells. Background. Activation of the cAMP signaling pathway by means of β2-adrenoceptor agonists has been shown to up-regulate interleukin-6 (IL-6) gene expression and to stimulate IL-6 production in macrophage cells. However, whether β2-adrenoceptor activation can also modify the rate of IL-6 production in macrophage cells activated by the bacterial endotoxins has not yet been determined. Using renal resident macrophage cells treated with endotoxin, lipopolysaccharide (LPS), and β2-adrenoceptor agonist, terbutaline, we investigated the role of cAMP pathway, tumor necrosis factor (TNF)-α and mitogen-activated protein kinase (MAPK) pathway (p42/p44) in regulating IL-6 production. Methods. IL-6 protein, mRNA, and promoter activity were measured in these cells exposed to LPS (1 μg/ml) and/or terbutaline (10-9 to 10-6 m). Furthermore, the time course effects of terbutaline on cAMP, MAPK (p42/p44), and TNF-α release were evaluated in the cells. Results. Terbutaline at high concentrations (10-6 m) significantly up-regulated IL-6 by approximately 25% (P < 0.05), whereas at a lower concentration (10-8 m), it down-regulated IL-6 production by 42% (P < 0.05). Terbutaline (10-8 and 10-6 m) caused a concentration- and time-dependent stimulation of cAMP (P < 0.05) and TNF production (P < 0.05) and a time-dependent decrease in MAPK activity (P < 0.05). Following the addition of a cAMP inhibitor, IL-6 promoter activity was correlated with TNF-α levels and MAPK activity. Conclusions. A biphasic effect of β2-adrenoceptor agonist on IL-6 production in renal resident macrophage cells became apparent when LPS was exposed to the cells. The terbutaline-induced down-regulation of IL-6 gene production was mediated by an inhibitory...
- Subjects
KIDNEY physiology; MACROPHAGES; INTERLEUKIN-6
- Publication
Kidney International, 1999, Vol 56, Issue 3, p839
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.1999.00630.x