1. Nuclear factor-kappaB regulates inflammatory cell apoptosis and phagocytosis in rat carrageenin-sponge implant model.
- Author
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Maiuri MC, Tajana G, Iuvone T, De Stefano D, Mele G, Ribecco MT, Cinelli MP, Romano MF, Turco MC, and Carnuccio R
- Subjects
- Animals, Blotting, Western, Cell Movement, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Immunohistochemistry, Inflammation drug therapy, Inflammation metabolism, Male, Neutrophils drug effects, Neutrophils ultrastructure, Nitrates analysis, Nitrites analysis, Oligonucleotides therapeutic use, Rats, Rats, Wistar, Time Factors, Transcription Factors therapeutic use, Transforming Growth Factor beta analysis, Transforming Growth Factor beta1, Apoptosis drug effects, Carrageenan toxicity, Inflammation chemically induced, NF-kappa B metabolism, Neutrophils metabolism, Phagocytosis drug effects
- Abstract
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.
- Published
- 2004
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