Seok-Yeong Yu^{1, 2}, Zhenhua Liu¹, Soonkyu Chung¹, Young-Cheul Kim^1,

Obesity-induced chronic inflammation contributes to the development of insulin resistance and type 2 diabetes and largely pertains to macrophages, primarily derived from bone marrow, (BMDMs) in insulin-sensitive tissues. Sulforaphane (SFN) is a major bioactive of cruciferous vegetables with a potent anti-inflammatory property. However, potential molecular modes of action remain unclear. The phosphorylation of nuclear factor-kappa B (NF-κB) and subsequent histone acetylation are critical signaling pathways for the transcription of pro-inflammatory genes in macrophages in obesity. Therefore, we tested our hypothesis that SFN mitigates the expression of pro-inflammatory genes in macrophages by suppressing p65 phosphorylation and histone acetylation using RAW 264.7 cell line and primary mouse BMDMs. In RAW 264.7 macrophages, SFN significantly inhibited the lipopolysaccharide (LPS)-induced pro-inflammatory genes expression, including iNos, Cox-2, Tnfα, Mcp-1 and Il-6, and suppressed CD11c immunofluorescence. Moreover, SFN significantly inhibited p65 phosphorylation and acetylation levels of histone H4, while it increased the histone deacetylase 3 (HDAC3) expression. Similarly, SFN inhibited p65 phosphorylation and histone H4 acetylation with HDAC3 expression increased in the BMDMs. These results revealed that SFN exerts anti-inflammatory effects via modulation of p65 phosphorylation and histone acetylation in macrophages. Our work suggests that supplementation of SFN or SFN-containing vegetables may serve as an anti-inflammatory diet component for mitigating obesity-related inflammation and related metabolic disorders.

Sulforaphane, NF-κB, RAW264.7 macrophage, bone marrow-derived macrophage, inflammation