Preprint Article Version 1 This version is not peer-reviewed

Sodium Acetate Enhances Neutrophil Extracellular Trap Formation via Histone Acetylation Pathway in Neutrophil-like HL-60 Cells

Version 1 : Received: 3 July 2024 / Approved: 3 July 2024 / Online: 3 July 2024 (07:55:14 CEST)

How to cite: Yasuda, H.; Takishita, Y.; Mortia, A.; Tsutsumi, T.; Nakagawa, N.; Sato, E. F. Sodium Acetate Enhances Neutrophil Extracellular Trap Formation via Histone Acetylation Pathway in Neutrophil-like HL-60 Cells. Preprints 2024, 2024070318. https://doi.org/10.20944/preprints202407.0318.v1 Yasuda, H.; Takishita, Y.; Mortia, A.; Tsutsumi, T.; Nakagawa, N.; Sato, E. F. Sodium Acetate Enhances Neutrophil Extracellular Trap Formation via Histone Acetylation Pathway in Neutrophil-like HL-60 Cells. Preprints 2024, 2024070318. https://doi.org/10.20944/preprints202407.0318.v1

Abstract

Neutrophil extracellular trap formation has been identified as a new cell death mediator, termed NETosis, which is distinct from apoptosis and necrosis. NETs capture foreign substances, such as bacteria, by releasing DNA into the extracellular environment, and have been associated with inflammatory diseases and altered immune responses. Short-chain fatty acids, such as acetate, are produced by the gut microbiota and reportedly enhance innate immune responses; however, the underlying molecular mechanisms remain unclear. Here, we investigated the effects of sodium acetate, which has the highest SCFA concentration in the blood and gastrointestinal tract, on NETosis by focusing on the mechanisms associated with histone acetylation in neutrophil-like HL-60 cells. Sodium acetate enhanced NETosis as shown by fluorescence staining with SYTOX green, and the effect was directly proportional to the treatment duration (16–24 h). Moreover, the addition of sodium acetate significantly enhanced the acetylation of Ace-H3, H3K9ace, H3K14ace, and H3K27ace. Sodium acetate-induced histone acetylation rapidly decreased upon stimulation with the calcium ionophore A23187, whereas histone citrullination markedly increased. These results demonstrate that sodium acetate induces NETosis via histone acetylation in neutrophil-like HL-60 cells, providing new insights into the therapeutic effects based on the innate immunity-enhancing effect of dietary fiber.

Keywords

neutrophil extracellular trap; NETosis; acetate; peptidyl arginine deiminase 4; histone acetylation; histone citrullination; immune response

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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