Possible new role for NF-kappaB in the resolution of inflammation

Nat Med. 2001 Dec;7(12):1291-7. doi: 10.1038/nm1201-1291.

Abstract

Inflammation involves the sequential activation of signaling pathways leading to the production of both pro- and anti-inflammatory mediators. Although much attention has focused on pro-inflammatory pathways that initiate inflammation, relatively little is known about the mechanisms that switch off inflammation and resolve the inflammatory response. The transcription factor NF-kappaB is thought to have a central role in the induction of pro-inflammatory gene expression and has attracted interest as a new target for the treatment of inflammatory disease. We show here that NF-kappaB activation in leukocytes recruited during the onset of inflammation is associated with pro-inflammatory gene expression, whereas such activation during the resolution of inflammation is associated with the expression of anti-inflammatory genes and the induction of apoptosis. Inhibition of NF-kappaB during the resolution of inflammation protracts the inflammatory response and prevents apoptosis. This suggests that NF-kappaB has an anti-inflammatory role in vivo involving the regulation of inflammatory resolution.

MeSH terms

  • Animals
  • Anti-Infective Agents / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / metabolism*
  • Apoptosis*
  • Carrageenan / adverse effects
  • Cysteine Endopeptidases
  • Female
  • Granuloma / chemically induced
  • Granuloma / immunology*
  • Inflammation
  • Leukocytes / immunology*
  • Leupeptins / pharmacology
  • Male
  • Mice
  • Multienzyme Complexes / antagonists & inhibitors
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Nitriles
  • Pleurisy / chemically induced
  • Pleurisy / immunology*
  • Proteasome Endopeptidase Complex
  • Protein Binding / drug effects
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2*
  • Pyrrolidines / pharmacology
  • Rats
  • Sulfones
  • Thiocarbamates / pharmacology
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta1
  • Tumor Suppressor Protein p53 / biosynthesis
  • bcl-2-Associated X Protein

Substances

  • Anti-Infective Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • BAY 11-7085
  • Leupeptins
  • Multienzyme Complexes
  • NF-kappa B
  • Nitriles
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Pyrrolidines
  • Sulfones
  • Tgfb1 protein, mouse
  • Tgfb1 protein, rat
  • Thiocarbamates
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • pyrrolidine dithiocarbamic acid
  • Carrageenan
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde