Nickel ions selectively inhibit lipopolysaccharide-induced interleukin-6 production by decreasing its mRNA stability.
Nickel ions selectively inhibit lipopolysaccharide-induced interleukin-6 production by decreasing its mRNA stability.
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DOI：
10.1371/journal.pone.0119428
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Hirasawa N
中科院分区：
文献类型：
--
作者：
Asakawa S;Kishimoto Y;Takano T;Okita K;Takakuwa S;Sato T;Hiratsuka M;Takeuchi O;Hirasawa N
镍离子很容易从许多合金中洗脱出来，并引发炎症和过敏。此前的研究表明，植入医疗器械引起的感染会引起炎症，并增强镍离子(Ni2+)的洗脱。然而，感染和Ni2+诱导的信号通路之间的串扰尚未被详细阐明。在本研究中，我们在BALB/c小鼠和小鼠巨噬细胞系RAW264的气囊型炎症模型中，研究了Ni2+对内毒素(LPS)诱导的细胞因子产生的影响。结果表明，Ni2+在体内和体外均能抑制脂多糖诱导的IL-6的产生，但对肿瘤坏死因子-α的产生无明显影响。钴离子(Co2+)对IL-6的产生也有抑制作用，但对氯离子(Cl-)、锌离子(Zn2+)、钯离子(Pd2+)无抑制作用，且对IL-6的产生具有高度的选择性。Ni2+不抑制ERK1/2、p38MAPK和JNK的激活。Ni2+虽然降低了IL-6的mRNA水平，但不能抑制内毒素诱导的IL-6启动子的激活。使用转录抑制剂放线菌素D的实验表明，Ni2+降低了IL-6mRNA的稳定性。此外，Ni2+抑制脂多糖诱导的Arid5a的表达，但不抑制regnase-1的表达。这些结果表明，Ni2+可能通过降低依赖Arid5a的IL-6mRNA的稳定性而选择性地抑制内毒素诱导的IL-6的产生。
Nickel (Ni) ions easily elute from many alloys and elicit inflammation and allergies. Previous studies have shown that infections due to the implantation of medical devices cause inflammation and enhance the elution of Ni ions (Ni2+). However, cross-talk between infection- and Ni2+-induced signaling pathways has not yet been elucidated in detail. In the present study, we investigated the effects of Ni2+ on the lipopolysaccharide (LPS)-induced production of cytokines in a LPS-induced air pouch-type inflammation model in BALB/c mice and the murine macrophage cell line RAW264. We demonstrated that Ni2+ inhibited the LPS-induced production of interleukin (IL)-6, but not that of tumor necrosis factor (TNF)-α both in vivo and in vitro. This inhibitory effect was also observed with cobalt ion (Co2+), but not with chloride ion (Cl-), zinc ion (Zn2+), or palladium ion (Pd2+), and was highly selective to the production of IL-6. Ni2+ did not inhibit the activation of ERK1/2, p38 MAPK, or JNK. Although Ni2+ decreased IL-6 mRNA levels, it failed to inhibit the LPS-induced activation of the IL-6 promoter. An experiment using actinomycin D, a transcription inhibitor, revealed that Ni2+ decreased the stability of IL-6 mRNA. Moreover, Ni2+ inhibited the LPS-induced expression of Arid5a, but not regnase-1. These results demonstrated that Ni2+ may have selectively inhibited the LPS-induced production of IL-6 by decreasing the Arid5a-dependent stabilization of IL-6 mRNA.
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影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
14.2
作者：
Larsen, Jeppe Madura;Bonefeld, Charlotte Menne;Skov, Lone
通讯作者：
Skov, Lone
DOI：
10.1084/jem.20090560
发表时间：
2009-08-31
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kimura A;Naka T;Nakahama T;Chinen I;Masuda K;Nohara K;Fujii-Kuriyama Y;Kishimoto T
通讯作者：
Kishimoto T
影响因子：
3.4
作者：
Heiss, K;Junkes, C;Thierse, HJ
通讯作者：
Thierse, HJ