Interleukin-33 stimulates formation of functional osteoclasts from human CD14(+) monocytes. 2010

Se Hwan Mun, and Na Young Ko, and Hyuk Soon Kim, and Jie Wan Kim, and Do Kyun Kim, and A-Ram Kim, and Seung Hyun Lee, and Yong-Gil Kim, and Chang Keun Lee, and Seoung Hoon Lee, and Bo Kyung Kim, and Michael A Beaven, and Young Mi Kim, and Wahn Soo Choi
Institute of Biomedical Sciences and Technology, Konkuk University, Chungju, Korea.

Interleukin (IL)-33 is a recently described pro-inflammatory cytokine. Here we demonstrate IL-33 as a regulator of functional osteoclasts (OCs) from human CD14(+) monocytes. IL-33 stimulates formation of tartrate-resistant acid phosphatase (TRAP)(+) multinuclear OCs from monocytes. This action was suppressed by anti-ST2 antibody, suggesting that IL-33 acts through its receptor ST2, but not by the receptor activator of NF-κB ligand (RANKL) decoy, osteoprotegerin, or anti-RANKL antibody. IL-33 stimulated activating phosphorylations of signaling molecules in monocytes that are critical for OC development. These included Syk, phospholipase Cγ2, Gab2, MAP kinases, TAK-1, and NF-κB. IL-33 also enhanced expression of OC differentiation factors including TNF-α receptor-associated factor 6 (TRAF6), nuclear factor of activated T cells cytoplasmic 1, c-Fos, c-Src, cathepsin K, and calcitonin receptor. IL-33 eventually induced bone resorption. This study suggests that the osteoclastogenic property of IL-33 is mediated through TRAF6 as well as the immunoreceptor tyrosine-based activation motif-dependent Syk/PLCγ pathway in human CD14(+) monocytes.

UI MeSH Term Description Entries
D007378 Interleukins Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. Interleukin
D009000 Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Monocyte
D010010 Osteoclasts A large multinuclear cell associated with the BONE RESORPTION. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in CEMENTUM resorption. Odontoclasts,Cementoclast,Cementoclasts,Odontoclast,Osteoclast
D011956 Receptors, Cell Surface Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands. Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D001862 Bone Resorption Bone loss due to osteoclastic activity. Bone Loss, Osteoclastic,Osteoclastic Bone Loss,Bone Losses, Osteoclastic,Bone Resorptions,Loss, Osteoclastic Bone,Losses, Osteoclastic Bone,Osteoclastic Bone Losses,Resorption, Bone,Resorptions, Bone
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000067596 Interleukin-33 A member of the INTERLEUKIN-1 protein family involved in the maturation of TH2 CELLS and the activation of MAST CELLS; BASOPHILS; EOSINOPHILS and NK CELLS. It is also produced by ENDOTHELIAL CELLS; EPITHELIAL CELLS and FIBROBLASTS; where it can function as an alarmin to modulate immune and inflammatory responses to tissue damage. IL-33,IL33,Interleukin 33
D000072179 Interleukin-1 Receptor-Like 1 Protein A receptor for INTERLEUKIN-33 that is related structurally to the interleukin-1 receptor. It contains three extracellular IMMUNOGLOBULIN-LIKE DOMAIN regions and associates with INTERLEUKIN-1 RECEPTOR ACCESSORY PROTEIN upon binding IL-33 to initiate signaling. It may function in the response of HELPER T CELLS to INFLAMMATION. IL1RL1 Protein,Interleukin 1 Receptor-Related Protein,Interleukin-33 Receptor,Interleukin 1 Receptor Like 1 Protein,Interleukin 1 Receptor Related Protein,Interleukin 33 Receptor,Receptor, Interleukin-33

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