Zoledronic acid enhances lipopolysaccharide-stimulated proinflammatory reactions through controlled expression of SOCS1 in macrophages.
Zoledronic acid enhances lipopolysaccharide-stimulated proinflammatory reactions through controlled expression of SOCS1 in macrophages.
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DOI：
10.1371/journal.pone.0067906
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Nakamura S
中科院分区：
文献类型：
--
作者：
Muratsu D;Yoshiga D;Taketomi T;Onimura T;Seki Y;Matsumoto A;Nakamura S
双膦酸盐相关性颌骨骨坏死（BRONJ）是使用含氮双膦酸盐（NBP）的严重副作用。许多研究表明，BRONJ仅限于颌骨，不会发生在其他骨骼。我们假设BRONJ与局部细菌感染有关，并涉及先天免疫系统。为了研究BRONJ与先天免疫之间的关系，我们检测了NBPs对巨噬细胞的影响，巨噬细胞是先天免疫的重要细胞类型之一。唑来膦酸（ZOL）预处理后的细胞中toll样受体-4 （TLR4）的表达与未处理的对照细胞无显著差异。然而，ZOL预处理后细胞因子水平和一氧化氮（NO）的产生增加。此外，ZOL通过增强i -κB -α降解诱导NF-κB活化。ZOL预处理后，脂多糖（LPS）诱导的细胞凋亡也增加。这种效应是由细胞因子信号传导抑制因子-1 （SOCS1）的减少介导的，SOCS1是骨髓分化主要反应基因88 （myd88）依赖信号传导的负调节因子。这些结果表明ZOL诱导了过度的先天免疫反应和促炎细胞因子的产生，这些过程可能参与了BRONJ中观察到的骨破坏。
Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious side effect of nitrogen-containing bisphosphonate (NBP) use. Many studies have shown that BRONJ is limited to the jawbone and does not occur in the other bones. We hypothesized that BRONJ is related to local bacterial iections and involves the innate immune system. To examine the relationship between BRONJ and innate immunity, we examined the effects of NBPs on macrophages, one of the important cell types in innate immunity. The expression of toll-like receptor-4 (TLR4) in cells after pretreatment with zoledronic acid (ZOL) did not considerably differ from that in untreated control cells. However, cytokine levels and nitric oxide (NO) production increased after pretreatment with ZOL. Furthermore, ZOL induced NF-κB activation by enhancing IκB-α degradation. Lipopolysaccharide (LPS)-induced apoptosis also increased after pretreatment with ZOL. This effect was mediated by a reduction of suppressor of cytokine signaling-1 (SOCS1), which is a negative regulator of myeloid differentiation primary response gene 88 (MyD 88)-dependent signaling. These results suggest that ZOL induced excessive innate immune response and proinflammatory cytokine production and that these processes may be involved in the bone destruction observed in BRONJ.
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影响因子：
11.4
作者：
Aliprantis, AO;Yang, RB;Zychlinsky, A
通讯作者：
Zychlinsky, A
DOI：
10.1056/nejmoa0903036
发表时间：
2010-03-18
期刊：
The New England journal of medicine
影响因子：
--
作者：
Greenberger S;Boscolo E;Adini I;Mulliken JB;Bischoff J
通讯作者：
Bischoff J
影响因子：
4.1
作者：
Patschan, D;Loddenkemper, K;Buttgereit, F
通讯作者：
Buttgereit, F
影响因子：
4.8
作者：
Saito, K;Yajima, T;Yoshikai, Y
通讯作者：
Yoshikai, Y
影响因子：
4.1
作者：
Favia, G.;Pilolli, G. P.;Maiorano, E.
通讯作者：
Maiorano, E.