Nuclear factor-kappaB regulates inflammatory cell apoptosis and phagocytosis in rat carrageenin-sponge implant model

Am J Pathol. 2004 Jul;165(1):115-26. doi: 10.1016/s0002-9440(10)63280-4.


In the present study we investigated whether apoptosis and phagocytosis are regulated by nuclear factor (NF)-kappaB in a model of chronic inflammation. The subcutaneous implant of lambda-carrageenin-soaked sponges elicited an inflammatory response, characterized by a time-related increase of leukocyte infiltration into the sponge and tissue formation, which was inhibited by simultaneous injection of wild-type oligodeoxynucleotide decoy to NF-kappaB. Molecular and morphological analysis performed on infiltrated cells demonstrated: 1) an inhibition of NF-kappaB/DNA binding activity; 2) an increase of polymorphonuclear leukocyte apoptosis correlated either to an increase of p53 or Bax and decrease of Bcl-2 protein expression; and 3) an increase of phagocytosis of apoptotic polymorphonuclear leukocytes by macrophages associated with an increase of transforming growth factor-beta1 and decrease of tumor necrosis factor-alpha as well as nitrite/nitrate production. Our results, showing that blockade of NF-kappaB by oligodeoxynucleotide decoy increases inflammatory cell apoptosis and phagocytosis, may contribute to lead to new insights into the mechanisms governing the inflammatory process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Blotting, Western
  • Carrageenan / toxicity*
  • Cell Movement
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Immunohistochemistry
  • Inflammation / chemically induced*
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Male
  • NF-kappa B / metabolism*
  • Neutrophils / drug effects
  • Neutrophils / metabolism*
  • Neutrophils / ultrastructure
  • Nitrates / analysis
  • Nitrites / analysis
  • Oligonucleotides / therapeutic use
  • Phagocytosis / drug effects*
  • Rats
  • Rats, Wistar
  • Time Factors
  • Transcription Factors / therapeutic use
  • Transforming Growth Factor beta / analysis
  • Transforming Growth Factor beta1


  • NF-kappa B
  • Nitrates
  • Nitrites
  • Oligonucleotides
  • Tgfb1 protein, rat
  • Transcription Factors
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Carrageenan