Isoproterenol inhibits Il-10, TNF-alpha, and nitric oxide production in RAW 264.7 macrophages.
In a previous study we have demonstrated in conscious endotoxemic mice that isoproterenol, a nonselective agonist of beta-adrenergic receptors, decreased the production of proinflammatory mediators tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO), and enhanced the formation of the anti-inflammatory cytokine interleukin-10 (IL-10). In the present study we investigated the effect of isoproterenol on the bacterial lipopolysaccharide (endotoxin, LPS; 10 microg/ml)-induced inflammatory response in RAW 264.7 macrophages in vitro. Pretreatment of cells with isoproterenol (10-300 microM) resulted in an inhibition of TNF-alpha, NO (reflected as its stable breakdown product nitrite), as well as IL-10 production that was paralleled with a restoration of the LPS-induced suppression of mitochondrial respiration. In addition, isoproterenol elevated cAMP accumulation in these cells. Finally, isoproterenol (300 microM) did not influence the nuclear translocation of nuclear factor kappaB. These data demonstrate that isoproterenol potently downregulates the LPS-induced inflammatory response and further support the notion that stimulation of beta-adrenoreceptors can be an effective strategy in the treatment of inflammatory diseases.
Haskó
G
G
Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest.
Németh
Z H
ZH
Szabó
C
C
Zsilla
G
G
Salzman
A L
AL
Vizi
E S
ES
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D003864:Depression, Chemical; D016753:Interleukin-10 / Q000096:biosynthesis*; D007545:Isoproterenol / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000318:Adrenergic beta-Agonists; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D000242:Cyclic AMP; D007545:Isoproterenol