Pathogenic role of natural killer T and natural killer cells in acetaminophen-induced liver injury in mice is dependent on the presence of dimethyl sulfoxide.
Pathogenic role of natural killer T and natural killer cells in acetaminophen-induced liver injury in mice is dependent on the presence of dimethyl sulfoxide.
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DOI：
10.1002/hep.22400
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发表时间：
2008-09
期刊：
影响因子：
13.5
通讯作者：
Pohl, Lance R.
中科院分区：
文献类型：
--
作者：
Masson, Mary Jane;Carpenter, Leah D.;Graf, Mary L.;Pohl, Lance R.
二甲基亚砜（DMSO）常用于生物研究中溶解溶解度低的药物和酶抑制剂。虽然DMSO通常被认为是相对惰性的，但它可以引起经常被忽视的生物效应。在最近的报告中发现了一个突出这一潜在问题的例子，该报告证明了NKT和NK细胞在C57 B1/6小鼠中对乙酰氨基酚诱导的肝损伤（AILI）中的致病作用，其中DMSO用于促进APAP溶解。我们在这里报告，NKT和NK细胞不发挥病理作用，在AILI在C57 B1/6小鼠在DMSO的情况下。虽然AILI在DMSO存在下在APAP处理之前在耗尽NKT和NK细胞的小鼠中显著减弱，但是当APAP溶解于盐水中时没有观察到这种效果。由于这一意外发现，随后研究了DMSO对肝NKT和NK细胞的影响。单独给药时，DMSO在体内激活肝脏NKT和NK细胞，这一点可以通过两种细胞类型中NKT细胞数量增加和细胞毒性效应分子干扰素（IFN）-γ和颗粒酶B的细胞内水平升高来证明。类似地，当用作APAP的溶剂时，DMSO再次增加NKT细胞数量并诱导两种细胞类型中的IFN-γ和颗粒酶B表达。总之，这些数据证明了DMSO对肝脏NKT和NK细胞的先前未被认识到的作用，表明在涉及这些细胞的实验中应谨慎使用DMSO。
Dimethyl sulfoxide (DMSO) is commonly used in biological studies to dissolve drugs and enzyme inhibitors with low solubility. While DMSO is generally thought of as being relatively inert, it can induce biological effects that are often overlooked. An example highlighting this potential problem is found in the recent report demonstrating a pathogenic role for NKT and NK cells in acetaminophen-induced liver injury (AILI) in C57Bl/6 mice in which DMSO was used to facilitate APAP dissolution. We report here that NKT and NK cells do not play a pathologic role in AILI in C57Bl/6 mice in the absence of DMSO. While AILI was significantly attenuated in mice depleted of NKT and NK cells prior to APAP treatment in the presence of DMSO, no such effect was observed when APAP was dissolved in saline. Due to this unexpected finding, the effects of DMSO on hepatic NKT and NK cells were subsequently investigated. When given alone, DMSO activated hepatic NKT and NK cells in vivo as evidenced by increased NKT cell numbers and higher intracellular levels of the cytotoxic effector molecules, interferon (IFN)-γ and granzyme B, in both cell types. Similarly, when used as a solvent for APAP, DMSO again increased NKT cell numbers and induced IFN-γ and granzyme B expression in both cell types. In conclusion, these data demonstrate a previously unappreciated effect of DMSO on hepatic NKT and NK cells, suggesting that DMSO should be used cautiously in experiments involving these cells.
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影响因子：
15.3
作者：
Kaneko, Y;Harada, M;Kawano, T;Yamashita, M;Shibata, Y;Gejyo, F;Nakayama, T;Taniguchi, M
通讯作者：
Taniguchi, M
DOI：
10.1111/j.1749-6632.1975.tb25345.x
发表时间：
1975-01-01
影响因子：
5.2
作者：
DENNIS, AJ;WILSON, HE
通讯作者：
WILSON, HE
影响因子：
4.1
作者：
Ju, C;Reilly, TP;Pohl, LR
通讯作者：
Pohl, LR
影响因子：
15.9
作者：
Halder, Ramesh C.;Aguilera, Carlos;Kumar, Vipin
通讯作者：
Kumar, Vipin
影响因子：
3.8
作者：
El-Hassan, H;Anwar, K;Kass, GEN
通讯作者：
Kass, GEN