Ahn Huijeong, Kim Jeeyoung, Lee Min-Jae, Kim Young Jin, Cho Young-Wook, Lee Geun-Shik
College of Veterinary Medicine, Kangwon National University, Chuncheon, Gangwon 200-701, Republic of Korea.
Korea Food Research Institute, Songnam, Kyeonggi 463-746, Republic of Korea.
Cytokine. 2015 Feb;71(2):223-31. doi: 10.1016/j.cyto.2014.11.001. Epub 2014 Nov 21.
Methylsulfonylmethane (MSM) is an organosulfur compound and the health benefits associated with MSM include inflammation. Although MSM has been shown to have various physiological effects, no study has yet focused on inflammasome activation. The inflammasome is a multiprotein complex that serves as a platform for caspase 1-dependent proteolytic maturation and secretion of interleukin-1β (IL-1β). In this study, we tested the effect of MSM on inflammasome activation using mouse and human macrophages. In our results, MSM significantly attenuated NLRP3 inflammasome activation in lipopolysaccharide-primed macrophages, although it had no effect on NLCR4 or AIM2 inflammasome activation. Extracts of MSM-enriched vegetables presented the same inhibitory effect on NLRP3 inflammasome activation as MSM. MSM also attenuated the transcriptional expression of IL-1α, IL-1β, IL-6, and NLRP3. Taken together, these results show that MSM has anti-inflammatory characteristics, interrupts NLRP3 inflammasome activation, and inhibits pro-cytokine expression. We further confirmed the intracellular mechanism of MSM in relation to NLRP3 inflammasome activation, followed by comparison with that of DMSO. Both chemicals showed a synergic effect on anti-NLRP3 activation and attenuated production of mitochondrial reactive oxygen species (ROS). Thus, MSM is a selective inhibitor of NLRP3 inflammasome activation and can be developed as a supplement to control several metabolic disorders.
二甲基砜（MSM）是一种有机硫化合物，与MSM相关的健康益处包括抗炎作用。尽管MSM已被证明具有多种生理效应，但尚未有研究聚焦于炎性小体激活。炎性小体是一种多蛋白复合物，作为半胱天冬酶1依赖性蛋白水解成熟和白细胞介素-1β（IL-1β）分泌的平台。在本研究中，我们使用小鼠和人类巨噬细胞测试了MSM对炎性小体激活的影响。在我们的结果中，MSM显著减弱了脂多糖预处理巨噬细胞中NLRP3炎性小体的激活，尽管它对NLCR4或AIM2炎性小体激活没有影响。富含MSM的蔬菜提取物对NLRP3炎性小体激活呈现出与MSM相同的抑制作用。MSM还减弱了IL-1α、IL-1β、IL-6和NLRP3的转录表达。综上所述，这些结果表明MSM具有抗炎特性，可中断NLRP3炎性小体激活，并抑制促细胞因子表达。我们进一步证实了MSM与NLRP3炎性小体激活相关的细胞内机制，随后与二甲基亚砜（DMSO）进行了比较。两种化学物质对抗NLRP3激活均显示出协同作用，并减弱了线粒体活性氧（ROS）的产生。因此，MSM是NLRP3炎性小体激活的选择性抑制剂，可开发为一种用于控制多种代谢紊乱的补充剂。
