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Interleukin-33 stimulates formation of functional osteoclasts from human CD14+ monocytes

2010; Springer Nature; Volume: 67; Issue: 22 Linguagem: Inglês

10.1007/s00018-010-0410-y

1420-9071

Se Hwan Mun, Na Young Ko, Hyuk Soon Kim, Jie Wan Kim, Do Kyun Kim, Aram Kim, Seung Hyun Lee, Yong‐Gil Kim, Chang Keun Lee, Seoung Hoon Lee, Bo Kyung Kim, Michael A. Beaven, Young Mi Kim, Wahn Soo Choi,

RNA Research and Splicing

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.