Sulforaphane Regulates Macrophage M1/M2 Polarization to Attenuate Macrophage-induced Caco-2 Cell Injury in an Inflammatory Environment

• Published in: Iranian journal of immunology Vol. 21; no. 1; pp. 37 - 52
• Main Authors: Yi, Ting, Liu, Zhiyin, Jia, Haokun, Liu, Qiongzhi, Peng, Jianjiao
• Format: Journal Article
• Language: English
• Published: Iran Shiraz Institute for Cancer Research 12-03-2024
• Subjects: Antioxidants; Biochemical analysis; Bone marrow; CD16 antigen; Cell activation; Cell injury; Cytokines; Electrical resistivity; Flow cytometry; Hospitals; Inflammation; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory diseases; Interleukins; Lipopolysaccharides; Macrophages; Pathogenesis; Phytochemicals; Polarization; Regulation; Sulforaphane; Tumor necrosis factor-TNF; Tumor necrosis factor-α; γ-Interferon; Nrf2/ARE; Inflammatory Bowel Disease; Sulforaphane; Macrophage
• ISSN: 1735-1383; 1735-367X
• DOI: 10.22034/iji.2024.98644.2580

The imbalance between M1 and M2 macrophage activation is closely associated with the pathogenesis of inflammatory bowel diseases (IBDs). Sulforaphane (SFN) plays an important role in the treatment of inflammatory diseases.
To investigate the effect of SFN on macrophage polarization and its underlying regulatory mechanism.
Mouse bone marrow-derived macrophages (BMDMs) were treated with SFN and an Nrf2 inhibitor, Brusatol. M1 macrophages were induced by LPS and IFN-γ stimulation, whereas M2 macrophages were induced by stimulation with IL-4 and IL-13. LPS-stimulated BMDMs were co-cultured with Caco-2 cells. Flow cytometry, qRT-PCR, and Western blot were performed to assess macrophage polarization. Cell function was assessed using CCK8 assay, transepithelial electrical resistance (TEER) assay, and biochemical analysis.
Higher concentrations of SFN resulted in better intervention effects, with an optimal concentration of 10 μM. SFN decreased the levels of IL-12, IL-6, and TNF-α, as well as the percentages of CD16/32 in M1 BMDMs. At the same time, SFN increased the levels of YM1, Fizz1, and Arg1 as well as the percentages of CD206+ cells in M2 BMDMs. In addition, SFN enhanced the accumulation of Nrf2, NQO1, and HO-1 in M1 BMDMs, and the downregulation of Nrf2 reversed the regulatory effect of SFN on M1/M2 macrophages. LPS-stimulated BMDMs induced Caco-2 cell damage, which was partially alleviated by SFN.
Our findings indicate that SFN may act as an Nrf2 agonist to regulate macrophage polarization from M1 to M2. Furthermore, SFN may represent a potential protective ingredient against IBD.