451. Interleukin-4 directly inhibits tumor necrosis factor-alpha-mediated osteoclast formation in mouse bone marrow macrophages.
- Author
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Kitaura H, Nagata N, Fujimura Y, Hotokezaka H, Tatamiya M, Nakao N, Yoshida N, and Nakayama K
- Subjects
- Acid Phosphatase metabolism, Animals, Bone Marrow drug effects, Carrier Proteins pharmacology, Cells, Cultured, Dose-Response Relationship, Drug, Humans, Isoenzymes metabolism, Macrophage Colony-Stimulating Factor pharmacology, Macrophages cytology, Membrane Glycoproteins pharmacology, Mice, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B, Tartrate-Resistant Acid Phosphatase, Tumor Necrosis Factor-alpha pharmacology, Bone Resorption, Cell Differentiation drug effects, Interleukin-4 pharmacology, Macrophages drug effects, Osteoclasts cytology, Osteoclasts drug effects, Tumor Necrosis Factor-alpha antagonists & inhibitors
- Abstract
Recently it has been found that osteoclast differentiation is induced by tumor necrosis factor (TNF)-alpha. Interleukin (IL)-4 was reported to suppress osteoclast differentiation and bone resorption. However, no study has investigated the effect of IL-4 on TNF-alpha-induced osteoclast formation. In this study, we investigated whether IL-4 inhibits TNF-alpha-mediated osteoclast formation in mouse bone marrow derived macrophages (BMM). First, IL-4 suppresses RANKL-induced osteoclast formation and bone resorption. Next, when BMM were cultured with TNF-alpha, osteoclast-like cells were formed. When they were cultured with both TNF-alpha and IL-4, osteoclast formation and bone resorption was suppressed by IL-4 in a dose-dependent manner. It has been recently found that TNF-alpha and RANKL synergistically promote osteoclastogenesis. Finally, we investigated whether IL-4 had the ability to inhibit synergistic TNF-alpha and RANKL-induced osteoclastogenesis, with the result that it effectively inhibited the synergistic osteoclast formation in a dose-dependent manner. We conclude that IL-4 can strongly inhibit osteoclast formation that is related to both physiological bone resorption induced by RANKL and pathological bone resorption induced by TNF-alpha.
- Published
- 2003
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