IL-33 inhibits RANKL-induced osteoclast formation through the regulation of Blimp-1 and IRF-8 expression
IL-33 inhibits RANKL-induced osteoclast formation through the regulation of Blimp-1 and IRF-8 expression
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DOI：
10.1016/j.bbrc.2015.03.033
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发表时间：
2015-05-01
影响因子：
3.1
通讯作者：
Nishihara, Tatsuji
中科院分区：
文献类型：
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作者：
Kiyomiya, Hiroyasu;Ariyoshi, Wataru;Nishihara, Tatsuji
白细胞介素33(IL-33)是新近发现的一种促炎细胞因子，属于IL-1家族。已有多项研究报道IL-33抑制破骨细胞分化。然而，IL-33调节破骨细胞生成的机制尚不清楚。在本研究中，我们检测了IL-33在体外对破骨细胞形成的影响。IL-33抑制核因子-kappaB受体激活剂(RANKL)和/或巨噬细胞刺激因子(M-CSF)诱导的小鼠骨髓细胞和单核/巨噬细胞系RAW264.7细胞破骨细胞的形成。IL-33还可抑制RANKL诱导的活化T细胞胞浆核因子1(NFATc1)的表达，从而降低组织蛋白酶K、破骨细胞刺激性跨膜蛋白(Oc-STAMP)和抗酒石酸酸性磷酸酶(Trap)等破骨细胞发生相关标志基因的表达。阻断IL-33-ST2结合可抑制IL-33对NFATc1的抑制作用。IL-33抑制RANKL诱导的B淋巴细胞诱导成熟蛋白-1(Blimp-1)的表达，随后抑制干扰素调节因子-8(IRF-8)等抗破骨细胞基因的表达。这些结果表明，IL-33-ST2相互作用通过调节Blimp-1和IRF-8的表达，下调RANKL诱导的NFATc1激活和破骨细胞分化。(C)2015 Elsevier Inc.保留所有权利。
Interleukin (IL)-33 is a recently discovered proinflammatory cytokine that belongs to the IL-1 family. Several studies have reported that IL-33 inhibits osteoclast differentiation. However, the mechanism of IL-33 regulation of osteoclastogenesis remains unclear. In the present study, we examined the effect of IL-33 on osteoclast formation in vitro. IL-33 suppressed osteoclast formation in both mouse bone marrow cells and monocyte/macrophage cell line RAW264.7 cells induced by receptor activator of NF-kappa B ligand (RANKL) and/or macrophage stimulating factor (M-CSF). IL-33 also inhibited the expression of RANKL-induced nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), thereby decreasing the expression of osteoclastogenesis-related marker genes, including Cathepsin K, Osteoclast stimulatory transmembrane protein (Oc-stamp) and Tartrate-resistant acid phosphatase (Trap). Blockage of IL-33-ST2 binding suppressed the IL-33-mediated inhibition of NFATc1. RANKL-induced B-lymphocyte-induced maturation protein-1 (Blimp-1) expression was also suppressed by IL-33, which was followed by the stimulation of anti-osteoclastic genes such as interferon regulatory factor-8 (IRF-8). These results suggest that IL-33-ST2 interactions down-regulate both RANKL-induced NFATc1 activation and osteoclast differentiation via the regulation of Blimp-1 and IRF-8 expression. (C) 2015 Elsevier Inc. All rights reserved.