Hofbauer, K. H. and Schoof, E. and Kurtz, Armin and Sandner, P. (2002) Inflammatory cytokines stimulate adrenomedullin expression through nitric oxide-dependent and -independent pathways. HYPERTENSION, 39 (1). pp. 161-167. ISSN 0194-911X
Full text not available from this repository. (Request a copy)Abstract
A body of evidence indicates that the production of adrenomedullin (ADM) in vivo is activated in states of inflammation. Our aim was to characterize the intracellular signaling pathways along which inflammation leads to a stimulation of ADM expression. For this purpose, we characterized the effects of inflammatory cytokines, tumor necrosis factor-alpha (100 mug/L), interleukin-1beta (20 mug/L), and interferon-gamma (0.5 U/L) on ADM gene expression in rat aortic vascular smooth muscle cells (AVSMCs). We found that inflammatory cytokines induced a time-dependent 12-fold upregulation of ADM mRNA in AVSMCs that was paralleled by a substantial increase in inducible NO synthase mRNA expression. The stimulatory effect of cytokines on ADM gene expression was attenuated by NO deprivation induced by Nomega-nitro-L-arginine methyl ester (1 mmol/L) and was in part mimicked by the NO donor S-nitroso-N-acetylpenicillamine (100 mumol/L). The cGMP analog 8-bromo-cGMP (100 mumol/L) had no effect on ADM gene expression, and inhibition of cGMP production by 1H-oxodiazolo-quinoxalin-1 (ODQ, 200 mumol/L) was not able to abrogate the increase of ADM mRNA induced by NO donation using S-nitroso-N-acetylpenicillamine (100 mumol/L). The significant induction of ADM gene expression by inflammatory cytokines and NO donation was also observed in mesangial cells, endothelial cells, and hepatocytes. These findings suggest that NO is a direct activator of ADM gene expression in a variety of cell types and that inflammatory cytokines stimulate ADM expression via both NO-dependent and -independent mechanisms. The stimulatory effect of NO appears to not be related to the classic guanylate cyclase-cGMP pathway.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SMOOTH-MUSCLE CELLS; TUMOR-NECROSIS-FACTOR; GENE-EXPRESSION; MESSENGER-RNA; PLASMA-LEVELS; FACTOR-ALPHA; RAT; MACROPHAGES; SECRETION; HYPOXIA; nitric oxide; adrenomedullin; cytokines; muscle, smooth, vascular |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Nov 2021 06:46 |
| Last Modified: | 16 Nov 2021 06:46 |
| URI: | https://pred.uni-regensburg.de/id/eprint/40747 |
Actions (login required)
 |
View Item |
