4.5 Article

Zoledronic acid exacerbates inflammation through M1 macrophage polarization

期刊

INFLAMMATION AND REGENERATION
卷 38, 期 -, 页码 -

出版社

BMC
DOI: 10.1186/s41232-018-0074-9

关键词

Zoledronic acid; Macrophage polarization; Inflammation

资金

  1. JSPS KAKENHI [16H05545, 15K11083]
  2. Grants-in-Aid for Scientific Research [15K11083, 16H05545] Funding Source: KAKEN

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Background: Zoledronic acid (Zol), one of the bisphosphonates, is frequently utilized for the treatment of osteoporosis and bone metastasis. However, the onset of medication-related osteonecrosis of the jaw (MRONJ) following dental treatments has become a serious issue. We reported previously that osteonecrosis can be induced by Zol and lipopolysaccharide (LPS) in vivo, suggesting the involvement of Zol in inflammation. Macrophages are divided into M1/M2 macrophages. M1 macrophages are involved in the induction and exacerbation of inflammation and express proinflammatory mediators including interleukin (IL)-1. On the other hand, M2 macrophages are associated with anti-inflammatory reactions through the expression of anti-inflammatory cytokines, such as IL-10. In the present study, we clarified the effects of Zol on M1/M2 macrophage polarization in vitro. Methods: Human monocytic THP-1 cells were polarized to macrophage-like cells by phorbol 12-myristate 13-acetate (PMA), and, after culturing for an additional 24 h with or without Zol, then polarized to M1 macrophages by LPS or to M2 macrophages by IL-4. Cell viability was examined by the WST-8 assay. Gene expression was confirmed by the real-time polymerase chain reaction. Protein expression was detected by western blotting and enzyme-linked immunosorbent assays. Results: Zol treatment upregulated the expression of IL-1 beta mRNA and protein through NLRP3 inflammasome activation in LPS-treated THP-1 cells. Zol treatment did not affect the expression of IL-10, IL-1ra, or CD206 in IL-4-treated THP-1 cells. Conclusions: Zol enhanced LPS-induced M1, but not M2, macrophage polarization through the NLRP3 inflammasome-dependent pathway, resulting in the production of inflammatory cytokines in THP-1 cells.

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