Narirutin Suppresses M1‑Related Chemokine InterferonGamma-Inducible Protein‑10 Production in Monocyte‑Derived M1 Cells via Epigenetic Regulation

Objective: We try to investigate this anti‑inflammatory effect of narirutin in human monocytic THP‑1‑derived M1 macrophage cells. Materials and Methods: To confirm our hypothesis, human THP‑1 cells (1 × 106 cells/mL) were initially treated with 20 ng/mL phorbol 12‑myristate 13‑acetate (PMA) for 24 h. The PMA‑differentiated THP‑1 cells were treated with various levels of narirutin 2 h before lipopolysaccharide stimulation; after that, the cells were cultured for 24–48 h and then examined. The concentration of interferon‑gamma‑inducible protein‑10 (IP‑10) was measured using enzyme‑linked immunosorbent assay. Epigenetic regulation mechanisms were explored by chromatin immunoprecipitation assay. Results: Narirutin significantly suppressed IP‑10 production in M1 macrophage cells, and the suppressing effect was partly reversed by the estrogen receptor antagonist, the aryl‑hydrocarbon receptor antagonist, the peroxisome proliferator‑activated receptor (PPAR)‑α antagonist, and the PPAR‑γ antagonist. We also found that narirutin‑induced IP‑10 suppression can be modulated by both histone H3 and H4 acetylation. Conclusion: Our study suggests the potential of narirutin for the treatment of inflammatory disease by suppressing IP‑10.