Dimethyl sulfoxide inhibits NLRP3 inflammasome activation

Immunobiology. 2014 Apr;219(4):315-22. doi: 10.1016/j.imbio.2013.11.003. Epub 2013 Nov 22.

Abstract

Dimethyl sulfoxide (DMSO) is an amphipathic molecule that is commonly/widely used as a solvent for biological compounds. In addition, DMSO has been studied as a medication for the treatment of inflammation, cystitis, and arthritis. Based on the anti-inflammatory characteristics of DMSO, we elucidated the effects of DMSO on activation of inflammasomes, which are cytoplasmic multi-protein complexes that mediate the maturation of interleukin (IL)-1β by activating caspase-1 (Casp1). In the present study, we prove that DMSO attenuated IL-1β maturation, Casp1 activity, and ASC pyroptosome formation via NLRP3 inflammasome activators. Further, NLRC4 and AIM2 inflammasome activity were not affected, suggesting that DMSO is a selective inhibitor of the NLRP3 inflammasomes. The anti-inflammatory effect of DMSO was further confirmed in animal, LPS-endotoxin sepsis and inflammatory bowel disease models. In addition, DMSO inhibited LPS-mediating IL-1s transcription. Taken together, DMSO shows anti-inflammatory characteristics, attenuates NLRP3 inflammasome activation, and mediates inhibition of IL-1s transcription.

Keywords: Cytokine; DMSO; Inflammasome; Interleukin-1; Macrophages; NLRP3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • CARD Signaling Adaptor Proteins / metabolism
  • Calcium-Binding Proteins / metabolism
  • Carrier Proteins / metabolism*
  • Caspase 1 / metabolism
  • Cells, Cultured
  • DNA-Binding Proteins / metabolism
  • Dimethyl Sulfoxide / administration & dosage*
  • Disease Models, Animal
  • Humans
  • Inflammasomes / drug effects*
  • Inflammasomes / immunology
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / immunology*
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides / immunology
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Mice
  • Mice, Inbred C57BL
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Sepsis / drug therapy*
  • Sepsis / immunology

Substances

  • AIM2 protein, human
  • Anti-Inflammatory Agents
  • CARD Signaling Adaptor Proteins
  • Calcium-Binding Proteins
  • Carrier Proteins
  • DNA-Binding Proteins
  • Inflammasomes
  • Interleukin-1beta
  • Lipopolysaccharides
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRC4 protein, human
  • NLRP3 protein, human
  • Caspase 1
  • Dimethyl Sulfoxide