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2018 ; 38
(ä): 16
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Zoledronic acid exacerbates inflammation through M1 macrophage polarization
#MMPMID29977413
Kaneko J
; Okinaga T
; Hikiji H
; Ariyoshi W
; Yoshiga D
; Habu M
; Tominaga K
; Nishihara T
Inflamm Regen
2018[]; 38
(ä): 16
PMID29977413
show ga
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? 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.