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.
Institute of Biomedical Sciences and Technology, Konkuk University, Chungju, Korea.
Se Hwan
SH
Mun
Na Young
NY
Ko
Hyuk Soon
HS
Kim
Jie Wan
JW
Kim
Do Kyun
DK
Kim
A-Ram
AR
Kim
Seung Hyun
SH
Lee
Yong-Gil
YG
Kim
Chang Keun
CK
Lee
Seoung Hoon
SH
Lee
Bo Kyung
BK
Kim
Michael A
MA
Beaven
Young Mi
YM
Kim
Wahn Soo
WS
Choi
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