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Inflammation Research
Published in: Inflammation Research 6/2013

01-06-2013 | Original Research Paper

Concentration dependent anti-inflammatory effects thrombin on polyphosphate-mediated inflammatory responses in vitro and in vivo

Authors: Sae-Kwang Ku, Jong-Sup Bae

Published in: Inflammation Research | Issue 6/2013

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Abstract

Aim and objective

Recent results indicate that polyphosphate (polyP) released by human endothelial cells can function as a pro-inflammatory mediator, and it has been reported that low thrombin concentrations mediate anti-inflammatory activities. This study was undertaken to investigate whether low thrombin concentrations can modulate polyP-mediated inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice.

Methods

Concentration dependent anti-inflammatory effects of thrombin such as barrier protection, inhibition of cell adhesion molecule expression and inhibition of monocytes adhesion and migration toward human endothelial cells against polyP-mediated pro-inflammatory activities were tested in vitro and in vivo. The concentration-dependent effects of thrombin on polyP-induced nuclear factor (NF)-κB activation and the production of tumor necrosis factor (TNF)-α and interleukin (IL)-6 were also tested.

Results

We found that at low concentrations (25–75 pM), thrombin inhibits polyP-mediated barrier disruption, the expressions of cell adhesion molecules, and leukocyte to HUVEC adhesion/migration. Interestingly, polyP-induced NF-κB activation and the production of TNF-α and IL-6 were inhibited by low thrombin concentrations in HUVECs. These anti-inflammatory functions of thrombin were confirmed in polyP-injected mice.

Conclusion

These results suggest that thrombin at 25–75 pM may have therapeutic potential for various systemic inflammatory diseases.
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Metadata
Title
Concentration dependent anti-inflammatory effects thrombin on polyphosphate-mediated inflammatory responses in vitro and in vivo
Authors
Sae-Kwang Ku
Jong-Sup Bae
Publication date
01-06-2013
Publisher
SP Birkhäuser Verlag Basel
Published in
Inflammation Research / Issue 6/2013
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-013-0613-4

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