Nuclear Factor-κB Regulates Inflammatory Cell Apoptosis and Phagocytosis in Rat Carrageenin-Sponge Implant Model

In the present study we investigated whether apoptosis and phagocytosis are regulated by nuclear factor (NF)-κB in a model of chronic inflammation. The subcutaneous implant of λ-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-κB. Molecular and morphological analysis performed on infiltrated cells demonstrated: 1) an inhibition of NF-κB/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-β1 and decrease of tumor necrosis factor-α as well as nitrite/nitrate production. Our results, showing that blockade of NF-κB by oligodeoxynucleotide decoy increases inflammatory cell apoptosis and phagocytosis, may contribute to lead to new insights into the mechanisms governing the inflammatory process.