Interleukin-33 stimulates formation of functional osteoclasts from human CD14(+) monocytes.
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.
Mun
Se Hwan
SH
Institute of Biomedical Sciences and Technology, Konkuk University, Chungju, Korea.
Ko
Na Young
NY
Kim
Hyuk Soon
HS
Kim
Jie Wan
JW
Kim
Do Kyun
DK
Kim
A-Ram
AR
Lee
Seung Hyun
SH
Kim
Yong-Gil
YG
Lee
Chang Keun
CK
Lee
Seoung Hoon
SH
Kim
Bo Kyung
BK
Beaven
Michael A
MA
Kim
Young Mi
YM
Choi
Wahn Soo
WS
D001862:Bone Resorption / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000276:immunology*; D009000:Monocytes / Q000166:cytology* / Q000276:immunology; D010010:Osteoclasts / Q000166:cytology* / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology*
C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D018950:Lipopolysaccharide Receptors; D011956:Receptors, Cell Surface