During Gram-negative sepsis, lipopolysaccharide (LPS) activates toll-like receptor (TLR) 4 and induces complex responses of\r\nimmune system and coagulation. However, the underlying LPS signalling mechanism on coagulation activation remains complex.\r\nTo determine the role of the intracellular signalling factors p38 mitogen-activated protein kinase (MAPK), nuclear factor-kappa\r\nB (NF-?B), and c-Jun N-terminal kinase (JNK) in the procoagulant response to LPS, coagulation process of human whole\r\nblood exposed to specific inhibitors was measured by thrombelastography. Samples were stimulated with LPS (100 �µg/mL) after\r\npreincubation with BAY117082 (specific NF-?B inhibitor), SP600125 (specific JNK inhibitor), SB203580 (specific p38 MAPK\r\ninhibitor), or vehicle. SB203580 strongly inhibited LPS-induced coagulation activation, whereas BAY117082 and SP600125 showed\r\nno significant effect. Activation of p38 MAPK, NF-?B, and JNK and respective inhibitory effects were confirmed by Multi-Target\r\nSandwich ELISA. In conclusion, activation of p38 MAPK is crucial for early LPS-induced activation of coagulation.
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