About this Journal Submit a Manuscript Table of Contents
ISRN Hematology
Volume 2012 (2012), Article ID 762614, 5 pages
http://dx.doi.org/10.5402/2012/762614
Research Article

Inhibition of LPS-Induced Activation of Coagulation by p38 MAPK Inhibitor

1Division of Neonatology, Department of Paediatrics, Medical School, University of Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany
2Department of Anesthesiology, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany
3Department of Anesthesiology, University of Giessen, Rudolf-Buchheim-Str. 7, 35392 Giessen, Germany

Received 5 December 2011; Accepted 27 December 2011

Academic Editors: L. Bordin and K. Oritani

Copyright © 2012 Lutz Koch et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

During Gram-negative sepsis, lipopolysaccharide (LPS) activates toll-like receptor (TLR) 4 and induces complex responses of immune system and coagulation. However, the underlying LPS signalling mechanism on coagulation activation remains complex. To determine the role of the intracellular signalling factors p38 mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), and c-Jun N-terminal kinase (JNK) in the procoagulant response to LPS, coagulation process of human whole blood exposed to specific inhibitors was measured by thrombelastography. Samples were stimulated with LPS (100 μg/mL) after preincubation with BAY117082 (specific NF-κB inhibitor), SP600125 (specific JNK inhibitor), SB203580 (specific p38 MAPK inhibitor), or vehicle. SB203580 strongly inhibited LPS-induced coagulation activation, whereas BAY117082 and SP600125 showed no significant effect. Activation of p38 MAPK, NF-κB, and JNK and respective inhibitory effects were confirmed by Multi-Target Sandwich ELISA. In conclusion, activation of p38 MAPK is crucial for early LPS-induced activation of coagulation.