IL-18 induces apoptosis of adherent bone marrow cells in TNF-alpha mediated osteoclast formation in synergy with IL-12.
It has recently been reported that TNF-alpha has the ability to accelerate osteoclastogenesis. We previously reported that the proinflammatory cytokine IL-12 induced apoptosis in TNF-alpha-mediated osteoclastogenesis in mouse bone marrow culture through an interaction of Fas and Fas ligand (FasL). In this study, the effect of IL-18 was investigated, which is also a proinflammatory cytokine, on TNF-alpha-mediated osteoclastogenesis. When mouse bone marrow cells were cultured with both TNF-alpha and IL-18, the number of adherent cells in the culture decreased. Apoptotic effects, indicated by nuclear, cellular and DNA fragmentation, were observed in the adherent cells. The apoptosis was inhibited by an anti-FasL antibody. Apoptosis of the adherent bone marrow cells might be caused by Fas-FasL interactions. Furthermore, IL-18 and IL-12 synergistically induced apoptosis of adherent bone marrow cells in the presence of TNF-alpha, and up-regulated FasL transcription in non-adherent cells. The results suggested that FasL synergistically up-regulated by IL-12 and IL-18 increased apoptosis of the adherent cells.
Kitaura
Hideki
H
Department of Developmental and Reconstructive Medicine, Division of Orthodontic and Biomedical Engineering, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan. kitaura@net.nagasaki-u.ac.jp
Tatamiya
Mutsuhito
M
Nagata
Noriko
N
Fujimura
Yuji
Y
Eguchi
Toshiko
T
Yoshida
Noriaki
N
Nakayama
Koji
K
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001854:Bone Marrow Cells / Q000502:physiology; D053938:DNA Fragmentation / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology*; D020382:Interleukin-18 / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D010010:Osteoclasts / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D020382:Interleukin-18; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12