Sulforaphane attenuates activation of NLRP3 and NLRC4 inflammasomes but not AIM2 inflammasome

Cell Immunol. Aug-Sep 2016;306-307:53-60. doi: 10.1016/j.cellimm.2016.07.007. Epub 2016 Jul 12.

Abstract

Sulforaphane (SFN), a compound within the isothiocyanate group of organosulfur compounds originating from cruciferous vegetables, has gained attention for its antioxidant, anti-inflammatory, and cancer chemopreventive properties. However, the effects of SFN on inflammasomes, which are multi-protein complexes that induce maturation of interleukin (IL)-1β, have been poorly studied. In this study, we investigated the effects of SFN on the assembly of NLRP3, NLRC4, and AIM2 inflammasomes as well as on the priming step of NLRP3 inflammasome in murine macrophages. In our results, SFN attenuated activation of NLRP3 and NLRC4 inflammasomes but not AIM2 inflammasome. In addition, SFN blocked expression of the NLRP3 gene and pro-IL-1β during the priming step. SFN further attenuated IL-1β secretion of monosodium uric acid-induced peritonitis in mice. Lastly, SFN inhibited generation of mitochondrial reactive oxygen species, which trigger NLRP3 inflammasome activation. Thus, SFN is suggested as an anti-inflammasome molecule for NLRP3 and NLRC4 inflammasome activation.

Keywords: AIM2; Inflammasome; NLRC4; NLRP3; Sulforaphane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Apoptosis Regulatory Proteins / metabolism
  • Brassicaceae / immunology
  • Calcium-Binding Proteins / metabolism
  • Cells, Cultured
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • Inflammasomes / metabolism
  • Isothiocyanates / pharmacology*
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / metabolism*
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Peritonitis / chemically induced
  • Peritonitis / drug therapy*
  • Peritonitis / immunology
  • Uric Acid

Substances

  • Aim2 protein, mouse
  • Anti-Inflammatory Agents
  • Apoptosis Regulatory Proteins
  • Calcium-Binding Proteins
  • DNA-Binding Proteins
  • Inflammasomes
  • Ipaf protein, mouse
  • Isothiocyanates
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Uric Acid
  • sulforafan