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

Interleukin-33 stimulates formation of functional osteoclasts from human CD14(+) monocytes.
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DOI:
10.1007/s00018-010-0410-y
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发表时间:
2010-11
影响因子:
8
通讯作者:
Choi, Wahn Soo
Choi, Wahn Soo
中科院分区:
生物学1区
文献类型:
--
作者:
Mun, Se Hwan;Ko, Na Young;Kim, Hyuk Soon;Kim, Jie Wan;Kim, Do Kyun;Kim, A-Ram;Lee, Seung Hyun;Kim, Yong-Gil;Lee, Chang Keun;Lee, Seoung Hoon;Kim, Bo Kyung;Beaven, Michael A.;Kim, Young Mi;Choi, Wahn Soo

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白细胞介素(IL)-33是最近描述的促炎细胞因子。在这里,我们证明了IL-33作为来自人CD 14+单核细胞的功能性破骨细胞(OC)的调节剂。IL-33刺激从单核细胞形成抗酒石酸酸性磷酸酶(TRAP)+多核OC。这种作用被抗ST 2抗体抑制,表明IL-33通过其受体ST 2发挥作用,而不是通过NF-κB配体受体激活剂(RANKL)诱饵、骨保护素或抗RANKL抗体发挥作用。IL-33刺激单核细胞中对OC发育至关重要的信号分子的活化磷酸化。这些包括Syk、磷脂酶Cγ2、Gab 2、MAP激酶、TAK-1和NF-κB。IL-33还增强OC分化因子的表达,包括TNF-α受体相关因子6(TRAF 6)、活化T细胞胞质核因子1、c-Fos、c-Src、组织蛋白酶K和降钙素受体。IL-33最终诱导骨吸收。这项研究表明,IL-33的破骨细胞生成特性是通过TRAF 6以及人CD 14+单核细胞中基于免疫受体酪氨酸的活化基序依赖性Syk/PLCγ途径介导的。
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.
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