Olive polyphenols attenuate TNF-α-stimulated M-CSF and IL-6 synthesis in osteoblasts: Suppression of Akt and p44/p42 MAP kinase signaling pathways - 03/09/21
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Abstract |
Background |
Olive oil polyphenols, which possess cytoprotective activities like anti-oxidant and anti-inflammatory effects, could modulate osteoblast functions. The aim of this study is to elucidate the effects and the underlying mechanisms of hydroxytyrosol and oleuropein on the tumor necrosis factor-α (TNF-α)-induced macrophage colony-stimulating factor (M-CSF) and interleukin-6 (IL-6) synthesis in osteoblasts.
Methods |
Osteoblast-like MC3T3-E1 cells were pretreated with hydroxytyrosol, oleuropein, deguelin, PD98059 or wedelolactone, and then stimulated by TNF-α. The levels of M-CSF and IL-6 in the conditioned medium were determined with ELISA. The mRNA expression levels of M-CSF or IL-6 were determined with real-time RT-PCR. The phosphorylation levels of Akt, p44/p42 mitogen-activated protein (MAP) kinase or NF-κB in the cell lysates were determined with Western blot analysis.
Results |
Hydroxytyrosol and oleuropein attenuated the TNF-α-stimulated M-CSF release. Deguelin, an inhibitor of Akt, significantly suppressed the TNF-α-stimulated M-CSF release, which failed to be affected by the MEK1/2 inhibitor PD98059 or the IκB inhibitor wedelolactone. Hydroxytyrosol and oleuropein suppressed the TNF-α-induced phosphorylation of Akt and p44/p42 MAP kinase. Hydroxytyrosol and oleuropein attenuated the TNF-α-stimulated IL-6 release. Hydroxytyrosol suppressed the TNF-α-induced mRNA expressions of M-CSF and IL-6. Hydroxytyrosol or oleuropein failed to affect the cell viability.
Conclusion |
Our present findings strongly suggest that olive oil polyphenols hydroxytyrosol and oleuropein down-regulates TNF-α signaling at the points upstream of Akt and p44/p42 MAP kinase in osteoblasts, leading to the attenuation of M-CSF and IL-6 synthesis.
Le texte complet de cet article est disponible en PDF.Highlights |
• | Hydroxytyrosol and oleuropein suppressed TNF-α-stimulated M-CSF and IL-6 release. |
• | Hydroxytyrosol suppressed TNF-α-induced mRNA expressions of M-CSF and IL-6. |
• | Not PD98059 but deguelin suppressed TNF-α-stimulated M-CSF release. |
• | Hydroxytyrosol and oleuropein suppressed TNF-α-induced Akt phosphorylation. |
• | Hydroxytyrosol and oleuropein suppressed TNF-α-induced p44/p42 MAPK phosphorylation. |
Abbreviations : M-CSF, NF-κB, RANK, RANKL, TNF-α, IL-6, MAP kinase, PI3-kinase, IκB, ELISA, RT-PCR, α-MEM, FBS
Keywords : Olive polyphenol, Macrophage colony-stimulating factor, Interleukin-6, Tumor necrosis factor-α, Osteoblast
Plan
Vol 141
Article 111816- septembre 2021 Retour au numéro
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