Premium
Catecholamines up‐regulate lipopolysaccharide‐induced IL‐6 production in human microvascular endothelial cells
Author(s) -
Gornikiewicz Alexander,
Sautner Thomas,
Brostjan Christine,
Schmierer Bernhard,
Függer Reinhold,
Roth Erich,
Mühlbacher Ferdinand,
Bergmann Michael
Publication year - 2000
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.14.9.1093
Subject(s) - lipopolysaccharide , microbiology and biotechnology , chemistry , immunology , medicine , biology
ABSTRACT 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 epi‐nephrine 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 cat‐echolamines and LPS could be reproduced in primary human skin microvascular endothelial cells. The cate‐cholamine‐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. Prein‐cubation with α and β receptor antagonists showed that the effect is mediated by β 1 ‐ and β 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., Sautner, T., Brostjan, C., Schmierer, B., Függer, R., Roth, E., Muhlbacher, F., Bergmann, M. Catecholamines up‐regu‐late lipopolysaccharide‐induced IL‐6 production in human microvascular endothelial cells. FASEB J. 14, 1093–1100 (2000)