• Shock · Mar 2023

    Valproic acid inhibits classical monocyte-derived tissue factor and alleviates hemorrhagic shock-induced acute lung injury in rats.

    • Lina Shao, Bing Wu, Chang Liu, and Wei Chong.
    • Emergency Department, the First Hospital of China Medical University, Shenyang, Liaoning Province, China.
    • Shock. 2023 Mar 1; 59 (3): 449459449-459.

    AbstractBackground: Monocytes and monocyte-derived tissue factor (TF) promote the development of sepsis-induced acute lung injury (ALI). Classical monocytes (C-Mcs) can be induced to express TF. Valproic acid (VPA) alleviates hemorrhagic shock (HS)-induced ALI (HS/ALI) and inhibits TF expression in monocytes. We hypothesized that C-Mcs and C-Mc-derived TF promoted HS/ALI and that VPA could inhibit C-Mc-derived TF expression and attenuate HS/ALI. Methods: Wistar rats and THP-1 cells were used to evaluate our hypothesis. Monocyte subtypes were analyzed by flow cytometry; mRNA expression was measured by fluorescence quantitative polymerase chain reaction; protein expression was measured by Western blotting, immunofluorescence, or immunohistology; inflammatory cytokines levels were measured by enzyme-linked immunosorbent assay; and ALI scores were used to determine the degree of ALI. Results: The blood %C-Mcs and C-Mcs/non-C-Mcs ratios, monocyte TF levels, serum and/or lung inflammatory cytokine levels, and ALI scores of HS rats were significantly increased ( P < 0.05). After monocyte depletion and thrombin inhibition, the inflammatory cytokine levels and ALI scores were significantly decreased ( P < 0.05). VPA reduced the %C-Mcs and C-Mc/non-C-Mc ratios, TF expression, inflammatory cytokine levels, and ALI scores during HS ( P < 0.05) and inhibited HS-induced monocyte Egr-1 and p-ERK1/2 expression ( P < 0.05). VPA inhibited hypoxia-induced TF expression in THP-1 cells by regulating the p-ERK1/2-Egr-1 axis. Conclusion: C-Mcs and C-Mc-derived TF accelerate the development of HS/ALI by increasing thrombin production. VPA inhibits HS-induced C-Mc production of TF by regulating the p-ERK1/2-Egr-1 axis and alleviates HS/ALI.Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Shock Society.

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