Catecholamines up‐regulate lipopolysaccharide‐induced IL‐6 production in human microvascular endothelial cells

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 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.

Acute mental stress elicits delayed increases in circulating inflammatory cytokine levels

“…In rodents, sympathetic nervous system activation during stress was associated with elevated plasma IL-6 levels [34]. Furthermore, adrenaline has been shown to induce an acute rise in plasma IL-6 levels [35]. These observations are also consistent with a possible role for catecholamines as mediators of the exercise-induced elevation of plasma IL-6 levels [36].…”

Pentoxifylline attenuates nociceptive sensitization and cytokine expression in a tibia fracture rat model of complex regional pain syndrome

“…(Gornikiewicz et al 2000) Also, it has been shown that terminal complement component mRNA levels could be increased in synovial cells and keratinocytes stimulated with various cytokines, whereas changes in complement protein levels could not be detected. (Guc et al 1993;Timar et al 2007) With a host of regulatory mechanisms controlling cytokine expression at the transcriptional, splicing, mRNA stability and translational levels, it is perhaps not surprising that fracture does not affect the levels of all cytokines in the same way.…”

A Membrane-Permeable Peptide Containing the Last 21 Residues of the GαSCarboxyl Terminus Inhibits GS-Coupled Receptor Signaling in Intact Cells: Correlations between Peptide Structure and Biological Activity

“…The ability of A42 to inhibit receptor-mediated cAMP production was also evaluated in HMEC-1, a human microvascular endothelial cell line, which constitutively expresses both A 2A and A 2B adenosine receptors (Feoktistov et al, 2002) and ␤-adrenergic receptors (Gornikiewicz et al, 2000). In this cell line, A 2B /A 2A mRNA ratio is approximately 4:1 (Feoktistov et al, 2002), whereas in PC12 cells, although both A 2A and A 2B mRNA were expressed (Arslan et al, 1999), the A 2A adenosine receptor seems to be the major adenosine receptor subtype involved in NECA-stimulated effector activation in some cellular clones (Arslan et al, 1999).…”