Cutting edge: CIAS1/cryopyrin/PYPAF1/NALP3/CATERPILLER 1.1 is an inducible inflammatory mediator with NF-kappa B suppressive properties

J Immunol. 2003 Dec 15;171(12):6329-33. doi: 10.4049/jimmunol.171.12.6329.

Abstract

Mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene have been recently linked to three chronic autoinflammatory disorders. These observations point to an important role for CIAS1 in regulating inflammatory processes. We report that TNF-alpha and ligands recognized by multiple Toll-like receptors rapidly induce CIAS1 gene expression in primary human monocytes. Transfection of full-length CIAS1 or either of two shorter, naturally occurring isoforms dramatically inhibited TNF-alpha-induced activation of NF-kappaB reporter activity. Furthermore, CIAS1 suppressed TNF-alpha-induced nuclear translocation of endogenous p65. Transcriptional activity of exogenous NF-kappaB p65 was also blocked by CIAS1. The nucleotide-binding and leucine-rich repeat regions, but not the pyrin domain of CIAS1, are responsible for this inhibition. These data suggest CIAS1/cryopyrin may act as a key regulator of inflammation, induced to dampen NF-kappaB-dependent proinflammatory signals.

MeSH terms

  • Active Transport, Cell Nucleus / immunology
  • Adjuvants, Immunologic / pharmacology
  • Amino Acid Sequence
  • Blood Proteins / biosynthesis
  • Blood Proteins / genetics
  • Blood Proteins / physiology*
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Cell Nucleus / immunology
  • Cell Nucleus / metabolism
  • Cytoplasm / immunology
  • Cytoplasm / metabolism
  • Genes, Reporter / immunology
  • HeLa Cells
  • Humans
  • Inflammation Mediators / metabolism
  • Inflammation Mediators / pharmacology*
  • Leucine-Rich Repeat Proteins
  • Lipopolysaccharides / pharmacology
  • Membrane Glycoproteins / physiology
  • Molecular Sequence Data
  • Monocytes / immunology
  • Monocytes / metabolism
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Protein Isoforms / biosynthesis
  • Protein Isoforms / physiology
  • Proteins / physiology
  • Receptors, Cell Surface / physiology
  • Repetitive Sequences, Amino Acid
  • Signal Transduction / immunology
  • Toll-Like Receptors
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / pharmacology
  • Tumor Necrosis Factor-alpha / physiology

Substances

  • Adjuvants, Immunologic
  • Blood Proteins
  • Carrier Proteins
  • Inflammation Mediators
  • Leucine-Rich Repeat Proteins
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Protein Isoforms
  • Proteins
  • Receptors, Cell Surface
  • Toll-Like Receptors
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha