title: Methylsulfonylmethane inhibits NLRP3 inflammasome activation.
abstract: 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.
authors.affiliation: College of Veterinary Medicine, Kangwon National University, Chuncheon, Gangwon 200-701, Republic of Korea.
authors.forename: Huijeong
authors.initials: H
authors.lastname: Ahn
authors.affiliation: College of Veterinary Medicine, Kangwon National University, Chuncheon, Gangwon 200-701, Republic of Korea.
authors.forename: Jeeyoung
authors.initials: J
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine, Kangwon National University, Chuncheon, Gangwon 200-701, Republic of Korea.
authors.forename: Min-Jae
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Korea Food Research Institute, Songnam, Kyeonggi 463-746, Republic of Korea.
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Korean Basic Science Institute, Chuncheon 200-701, Republic of Korea.
authors.forename: Young-Wook
authors.initials: YW
authors.lastname: Cho
authors.affiliation: College of Veterinary Medicine, Kangwon National University, Chuncheon, Gangwon 200-701, Republic of Korea. Electronic address: leegeun@kangwon.ac.kr.
authors.forename: Geun-Shik
authors.initials: GS
authors.lastname: Lee
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000276:immunology* / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000276:immunology; D006801:Humans; D015151:Immunoblotting; D058847:Inflammasomes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D053582:Interleukin-1alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008089:Listeria monocytogenes / Q000276:immunology / Q000502:physiology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008810:Mice, Inbred C57BL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012486:Salmonella typhimurium / Q000276:immunology / Q000502:physiology; D013450:Sulfones / Q000276:immunology* / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D002352:Carrier Proteins; D016207:Cytokines; D058847:Inflammasomes; D018836:Inflammation Mediators; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D017382:Reactive Oxygen Species; D013450:Sulfones; C025910:dimethyl sulfone; D004121:Dimethyl Sulfoxide
keywords: DMSO; Inflammasome; Interleukin-1beta; MSM; Macrophages