Xiang Yang, Zhao Ming-Ming, Sun Sujiao, Guo Xiao-Long, Wang Qiquan, Li Sheng-An, Lee Wen-Hui, Zhang Yun
Human Aging Research Institute and School of Life Sciences, Nanchang University, Nanchang, China.
Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650223, China.
Cytotechnology. 2018 Feb;70(1):313-320. doi: 10.1007/s10616-017-0145-9. Epub 2017 Sep 30.
Dimethyl sulfoxide (DMSO) is widely used in the laboratory and in clinical situations because it is soluble in both aqueous and organic media and can be used to treat many types of diseases. Thus, it is meaningful to assess the comprehensive and in-depth biological activities of DMSO. Here, we showed that a high concentration of DMSO induced pro-inflammatory cytokine interleukin-1β (IL-1β) secretion from the monocytic cell line THP-1. DMSO-induced IL-1β secretion was dependent on intracellular caspase-1 activation. Further study revealed that the activation of caspase-1 by DMSO relied on NLRP3 inflammasome formation. It is generally accepted that the NLRP3 inflammasome is activated by reactive oxygen species generation or potassium efflux; however, the common NLRP3 inflammasome trigger remains controversial. Here, we showed that although DMSO is a ROS scavenger, this chemical increases membrane permeability and potassium efflux, and the formation of the NLRP3 inflammasome reflects the increased membrane permeability and potassium efflux induced by DMSO. The present study reveals a new characteristic of DMSO, which should be considered when using this chemical in either the laboratory or the clinic.
二甲基亚砜(DMSO)在实验室和临床环境中被广泛使用,因为它可溶于水性和有机介质,并且可用于治疗多种类型的疾病。因此,评估DMSO的全面和深入的生物学活性具有重要意义。在此,我们表明高浓度的DMSO可诱导单核细胞系THP-1分泌促炎细胞因子白细胞介素-1β(IL-1β)。DMSO诱导的IL-1β分泌依赖于细胞内半胱天冬酶-1的激活。进一步研究表明,DMSO对半胱天冬酶-1的激活依赖于NLRP3炎性小体的形成。一般认为,NLRP3炎性小体通过活性氧生成或钾外流激活;然而,常见的NLRP3炎性小体触发因素仍存在争议。在此,我们表明,尽管DMSO是一种活性氧清除剂,但这种化学物质会增加膜通透性和钾外流,并且NLRP3炎性小体的形成反映了DMSO诱导的膜通透性增加和钾外流。本研究揭示了DMSO的一个新特性,在实验室或临床使用这种化学物质时应予以考虑。