Catecholamines up-regulate lipopolysaccharide-induced IL-6 production in human microvascular endothelial cells.
The catecholamine-mediated modulation of the cytokine network has primarily been demonstrated for leukocytes. Whereas catecholamines decrease the LPS-induced production of IL-6 by leukocytes, serum levels of IL-6 are dramatically increased by the catecholamine epinephrine in animal endotoxemia models. We now demonstrate that epinephrine as well as norepinephrine can induce IL-6 in an endothelial cell line (HMEC-1). Furthermore, these catecholamines could even potentiate the LPS-induced IL-6 protein production. The synergistic effect of catecholamines and LPS could be reproduced in primary human skin microvascular endothelial cells. The catecholamine-induced IL-6 stimulation is based on increased IL-6 mRNA levels. RNA stability assays revealed that this regulation is not a result of enhanced RNA stability and therefore is most likely due to an increased transcription. Treatment with cycloheximide indicated that new protein synthesis is not necessary for this transcriptional up-regulation of IL-6 mRNA. Preincubation with alpha and beta receptor antagonists showed that the effect is mediated by beta(1)- and beta(2)-adrenergic receptors. Thus, endothelial cells might be a possible source of increased IL-6 production observed in situations such as stress or septic shock, in which catecholamines are elevated due to endogenous production or exogenous application.
Gornikiewicz
A
A
Department of Surgery, University of Vienna, 1090 Vienna, Austria.
Sautner
T
T
Brostjan
C
C
Schmierer
B
B
Függer
R
R
Roth
E
E
Mühlbacher
F
F
Bergmann
M
M
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D002395:Catecholamines / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D012867:Skin / Q000098:blood supply; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D003513:Cycloheximide; D009638:Norepinephrine; D004837:Epinephrine