Dopamine suppresses IL-12 p40 production by lipopolysaccharide-stimulated macrophages via a beta-adrenoceptor-mediated mechanism.
In this study, we examined the effect of dopamine on the production of IL-12 p40 by lipopolysaccharide (LPS)-stimulated J774.1 macrophages and mouse peritoneal macrophages. Treatment of J774.1 cells with dopamine (0.01-100 microM) decreased the release of IL-12 p40, in a concentration-dependent manner. The attenuating effect of dopamine on IL-12 p40 production appeared to be pretranslational, because dopamine decreased mRNA accumulation of IL-12 p40. The inhibitory effect of dopamine on IL-12 p40 production by J774.1 macrophages was not mediated by dopamine receptors, because dopamine receptor antagonists were unable to reverse the dopamine-induced suppression of IL-12 p40 production. Since the beta-adrenoceptor antagonist propranolol completely prevented the inhibitory effect of dopamine on IL-12 p40 production, the suppressive effect of dopamine on IL-12 p40 production by J774.1 cells is mediated by beta-adrenoceptors. In contrast to J774.1 cells, propranolol only partially reversed the inhibitory effect of dopamine on IL-12 production by peritoneal macrophages. Furthermore, dopamine stimulated the production of the anti-inflammatory cytokine IL-10 in both J774.1 cells and peritoneal macrophages. While the stimulatory effect of dopamine on IL-10 production by J774.1 cells was beta-adrenoceptor-mediated, dopamine increased IL-10 production by peritoneal macrophages via both beta-adrenoceptor-dependent and independent mechanisms. These results indicate that dopamine has multiple anti-inflammatory effects mediated by both beta-adrenoceptor dependent and independent mechanisms.
Haskó
György
G
Department of Surgery, UMD-New Jersey Medical School, 185 South Orange Avenue, University Heights, Newark, NJ 07103, USA. haskoge@umdnj.edu
Szabó
Csaba
C
Németh
Zoltán H
ZH
Deitch
Edwin A
EA
D000818:Animals; D002478:Cells, Cultured; D004298:Dopamine / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D016753:Interleukin-10 / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D016753:Interleukin-10; D018664:Interleukin-12; D004298:Dopamine