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- W2806346456 abstract "Over-activated osteoclasts derived from myeloid or peripheral blood monocytes by inflammatory cytokines results in osteoporosis, osteoarthritis and other bone erosion related diseases. IL-35 is a novel anti-inflammatory and immunosuppressive factor. This study investigated the effect of IL-35 on TNF-α-induced osteoclastogenesis. In the presence of IL-35, this process was detected by TRAP staining, F-actin staining, and bone resorption assays. The effects of IL-35 on TNF-α-induced apoptosis were demonstrated by TUNEL staining, cell viability assays, and flow cytometry. Moreover, a microarray was performed to detect the effect of IL-35 on TNF-α-activated phosphatase kinase. The effect of IL-35 on the TNF-α-mediated activation of NF-κB, MAPK, TRAF2, RIP1, FADD, caspase8, and caspase3 was further investigated. In addition, a murine calvarial osteolysis model was established via the subcutaneous injection of TNF-α onto the calvaria, and histological analysis was subsequently performed. As a result, IL-35 inhibited TNF-α-induced osteoclast formation and bone resorption in vitro and osteolysis calvaria in vivo. NFATc1, c-fos, and TRAP were down-regulated by IL-35 through the inhibition of NF-κB and MAPK, during which JAK1/STAT1 was activated. Moreover, based on TUNEL staining and flow cytometry, IL-35 was shown to enhance TNF-α-induced osteoclast apoptosis. Meanwhile, FADD, cleaved-caspase 8, and cleaved-caspase 3 were increased in cells treated with TNF-α and IL-35, whereas the DNA binding activity of NF-κB, was increased in TNF-α-treated cells, but was decreased in cells treated with both TNF-α and IL-35. In conclusions, IL-35 inhibits TNF-α-induced osteoclastogenesis and promotes apoptosis by activating JAK1/STAT1 and shifting activation from TRADD-TRAF2/RIP1-NF-κB to TRADD-FADD-caspase 8 signaling." @default.
- W2806346456 created "2018-06-13" @default.
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- W2806346456 date "2018-01-01" @default.
- W2806346456 modified "2023-09-22" @default.
- W2806346456 title "IL-35 inhibits TNF-α-induced osteoclastogenesis and promotes apoptosis via shifting the activation from TRADD-TRAF2 to TRADD-FADD by JAK1/STAT1" @default.
- W2806346456 doi "https://doi.org/10.3389/fimmu.2018.01337" @default.
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