Ahn Huijeong, Kang Seung Goo, Yoon Sung-Il, Ko Hyun-Jeong, Kim Pyeung-Hyeun, Hong Eui-Ju, An Beum-Soo, Lee Eunsong, Lee Geun-Shik
College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon, Gangwon, 24341, Republic of Korea.
Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon, Gangwon, 24341, Republic of Korea.
Sci Rep. 2017 Sep 29;7(1):12409. doi: 10.1038/s41598-017-12635-6.
Methylene blue (MB), which has antioxidant, anti-inflammatory, neuroprotective, and mitochondria protective effects, has been widely used as a dye and medication. However, the effect of MB on inflammasome activation has not yet been studied. Inflammasomes are multi-protein complexes that induce maturation of interleukins (ILs)-1β and -18 as well as caspase-1-mediated cell death, known as pyroptosis. Dysregulation of inflammasomes causes several diseases such as type 2 diabetes, Alzheimer's disease, and gout. In this study, we assess the effect of MB on inflammasome activation in macrophages. As the result, MB attenuated activation of canonical inflammasomes such as NLRP3, NLRC4, and AIM2 as well as non-canonical inflammasome activation. In addition, MB inhibited upstream signals such as inflammasome assembly, phagocytosis, and gene expression of inflammasome components via inhibition of NF-κB signaling. Furthermore, MB reduced the activity of caspase-1. The anti-inflammasome properties of MB were further confirmed in mice models. Thus, we suggest that MB is a broad-spectrum anti-inflammasome candidate molecule.
亚甲蓝（MB）具有抗氧化、抗炎、神经保护和线粒体保护作用，已被广泛用作染料和药物。然而，MB对炎性小体激活的影响尚未得到研究。炎性小体是一种多蛋白复合物，可诱导白细胞介素（IL）-1β和-18成熟以及半胱天冬酶-1介导的细胞死亡，即细胞焦亡。炎性小体失调会引发多种疾病，如2型糖尿病、阿尔茨海默病和痛风。在本研究中，我们评估了MB对巨噬细胞中炎性小体激活的影响。结果显示，MB减弱了典型炎性小体如NLRP3、NLRC4和AIM2的激活以及非典型炎性小体的激活。此外，MB通过抑制NF-κB信号传导，抑制了炎性小体组装、吞噬作用和炎性小体成分的基因表达等上游信号。此外，MB降低了半胱天冬酶-1的活性。MB的抗炎性小体特性在小鼠模型中得到了进一步证实。因此，我们认为MB是一种广谱抗炎性小体候选分子。
