S100A8 and S100A9 induce cytokine expression and regulate the NLRP3 inflammasome via ROS-dependent activation of NF-κB(1.)

PLoS One. 2013 Aug 19;8(8):e72138. doi: 10.1371/journal.pone.0072138. eCollection 2013.


S100A8 and S100A9 are cytoplasmic proteins expressed by phagocytes. High concentrations of these proteins have been correlated with various inflammatory conditions, including autoimmune diseases such as rheumatoid arthritis and Crohn's disease, as well as autoinflammatory diseases. In the present study, we examined the effects of S100A8 and S100A9 on the secretion of cytokines and chemokines from PBMCs. S100A8 and S100A9 induced the secretion of cytokines such as IL-6, IL-8, and IL-1β. This secretion was associated with the activation and translocation of the transcription factor NF-κB. Inhibition studies using antisense RNA and the pharmacological agent BAY-117082 confirmed the involvement of NF-κB in IL-6, IL-8, and IL-1β secretion. S100A8- and S100A9-mediated activation of NF-κB, the NLR family, pyrin domain-containing 3 (NLRP3) protein, and pro-IL-1β expression was dependent on the generation of reactive oxygen species. This effect was synergistically enhanced by ATP, a known inflammasome activator. These results suggest that S100A8 and S100A9 enhance the inflammatory response by inducing cytokine secretion of PBMCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CARD Signaling Adaptor Proteins
  • Calgranulin A / physiology*
  • Calgranulin B / physiology*
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Cytoskeletal Proteins / metabolism
  • Gene Expression
  • Inflammasomes
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Lipopolysaccharides / pharmacology
  • NF-kappa B p50 Subunit / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Protein Transport
  • Reactive Oxygen Species / metabolism*
  • Transcription Factor RelA / metabolism
  • Transcriptional Activation


  • CARD Signaling Adaptor Proteins
  • Calgranulin A
  • Calgranulin B
  • Carrier Proteins
  • Cytokines
  • Cytoskeletal Proteins
  • Inflammasomes
  • Lipopolysaccharides
  • NF-kappa B p50 Subunit
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • PYCARD protein, human
  • RELA protein, human
  • Reactive Oxygen Species
  • Transcription Factor RelA