キョウチクトウ科植物由来抽出物による炎症促進性型M1マクロファージ活性化と破骨細胞分化の抑制

抄録

Macrophages play important roles in immune response and tissue homeostasis. In response to various extracellular stimuli, macrophages polarize and differentiate into subgroups such as M1 and M2 macrophages, and osteoclasts. Excessive M1 macrophage and osteoclast activation is associated with inflammatory diseases including rheumatoid arthritis. Here, we find the Apocynaceae plant (AP) extract suppresses LPS-induced M1 activation and RANKL-induced osteoclast differentiation in mouse bone marrow-derived macrophages. Expression levels of LPS-induced nitric oxide and pro-inflammatory cytokines such as TNF, IL-1β and IL-6 and RANKL-induced osteoclast marker genes such as NFATc1, CTSK, ACP5, DC-STAMP, ATP6V0D2 were suppressed by AP extract. AP extract inhibited LPS- and RANKL-induced phosphorylation of Akt and IκBα degradation. Furthermore, AP extract significantly reduced PDK1 kinase activity. Suppression of osteoclast differentiation by AP extract was partially rescued by a PDK1 activator PS-48. These results suggest that the inhibitory effects of AP extract on LPS-induced M1 macrophage polarization and RANKL-induced osteoclast differentiation are associated with suppression of PDK1-Akt-NF-κB signaling pathway and may provide an important information for developing new therapeutic agents for inflammatory diseases.