Molecular mechanisms of acetyltransferase/histone deacetylase involvement in high mobility group box 1 nucleoplasmic translocation in sepsis: A bioinformatics and experimental approach

High mobility group box 1 (HMGB1) nuclear‑cytoplasmic translocation is a key event in sepsis‑associated inflammation, but the upstream mechanisms regulating this process remain incompletely understood. The present study aimed to investigate the associations among C‑X‑C motif chemokine ligand 8 (CXCL8)‑PI3K/Akt signaling in HMGB1 nuclear‑cytoplasmic translocation and to examine concurrent acetyltransferase (HAT)/histone deacetylase (HDAC)‑associated changes under inflammatory conditions. RAW264.7 macrophages were stimulated with lipopolysaccharide (LPS) to induce septic conditions and HMGB1 subcellular localization was assessed using western blotting. In addition, HAT and HDAC enzymatic activities were measured using colorimetric activity assay kits. Bioinformatics analysis of sepsis‑associated datasets (GSE46955 and GSE57065) identified CXCL8 as a hypothesis‑generating candidate core gene. In an LPS/IFN‑γ‑induced THP‑1‑derived inflammatory macrophage model, HMGB1 nuclear‑cytoplasmic translocation was also observed, together with increased CXCL8, CREB‑binding protein and p300 mRNA levels, decreased HDAC1, HDAC2 and HDAC4 mRNA levels and activated Akt phosphorylation at Ser473. Representative western blotting results following treatment with the C‑X‑C motif chemokine receptor (CXCR)1/2 inhibitor Reparixin or the PI3K inhibitor LY294002 provided preliminary support for the potential involvement of CXCR1/2‑PI3K/Akt signaling in HMGB1 nuclear‑cytoplasmic translocation. Collectively, these findings support a potential role for CXCL8/CXCR1/2‑PI3K/Akt signaling in HMGB1 nuclear‑cytoplasmic translocation and provide complementary, hypothesis‑generating evidence associating HAT/HDAC‑related changes to this process.