Abstract Number: PB0731
Meeting: ISTH 2021 Congress
Background: Brain injury is associated with neuroinflammation, neurodegeneration, and also blood coagulation with thrombin formation and generation of activated protein C (APC).
Aims: In the present study we investigated the ability of APC to modulate the production of IL-1b and IL-6 by mast cells (MC), MC survival and NF-κBp65 translocation into MC nucleus in acute inflammation in rats and at glutamate(Glu)- induced toxicity in cultural neurons.
Methods: MC were isolated from the peritoneal cavity of thioglycolate broth-induced acute inflammation rats by Ficoll density gradient. IL-1b, 6 were analyzed using ELISA Kit. The translocation of NF-κBp65 to nucleus was analyzed by antiNF-κBp65 antibodies. MTT-test was used to evaluate cell viability.
Results: Thioglycolate injection induced inflammatory response with the rise of IL-1β and IL-6. MC IL-6 production was 1.3, 1.8 and 1.9-fold decreased by single intraperitoneal injection of 5nM APC at 0.5, 1.5 and 4h of inflammation, respectively. The enhanced production of IL-1β in MC under action of APC was also decreased. APC protected MC from death at 30 min of acute inflammation. The development of inflammation in rats led to activation of NF-κBp65. APC blocks the translocation of NF-κBp65 into the nucleus of MC. The maximal effect of APC was revealed in 1.5 h after induction of inflammation. APC at concentrations as low as 1–2 nM inhibits the translocation of NF-κBp65 into the nucleus of cultured rat hippocampal neurons, induced by 100 M Glu or 50 nM thrombin. The blocking effect of APC on NF-κBp65 translocation was observed at 1 and 4 h after cell treatment with Glu. The binding of APC to EPCR/PAR-1 is required to control NF-κB activation at Glu-toxicity and acute inflammation in rats.
Conclusions: Our data indicate that APC provides not only anti-apoptotic protection (in case of Glu-toxicity), but also antineuroinflammatory activity via decrease the nuclear level of NF-κBp65 in cells
To cite this abstract in AMA style:Gorbacheva L, Ivanova A. Activated Protein C Impacts Survival and Activity of Mast Cells and Neurons via the Modulation of Nuclear Factor-κB Activation [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/activated-protein-c-impacts-survival-and-activity-of-mast-cells-and-neurons-via-the-modulation-of-nuclear-factor-%ce%bab-activation/. Accessed September 29, 2023.
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