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(American Journal of Pathology. 2004;165:115-126.)
© 2004 American Society for Investigative Pathology

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

Maria Chiara Maiuri^*, Gianfranco Tajana, Teresa Iuvone^*, Daniela De Stefano^*, Guido Mele, Maria Teresa Ribecco, Maria Pia Cinelli, Maria Fiammetta Romano^¶, Maria Caterina Turco and Rosa Carnuccio^*

From the Dipartimento di Farmacologia Sperimentale,^* Scienze Biomorfologiche, and Biochimica e Biotecnologie Mediche,^¶ Università degli Studi di Napoli "Federico II," Napoli; the Dipartimento di Scienze Farmaceutiche, Università degli Studi di Salerno, Fisciano (SA); and the Dipartimento di Oncologia Sperimentale, Istituto Nazionale Tumori Fondazione "G. Pascale," Napoli, Italy

In the present study we investigated whether apoptosis and phagocytosis are regulated by nuclear factor (NF)-B in a model of chronic inflammation. The subcutaneous implant of -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-B. Molecular and morphological analysis performed on infiltrated cells demonstrated: 1) an inhibition of NF-B/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-ß1 and decrease of tumor necrosis factor- as well as nitrite/nitrate production. Our results, showing that blockade of NF-B by oligodeoxynucleotide decoy increases inflammatory cell apoptosis and phagocytosis, may contribute to lead to new insights into the mechanisms governing the inflammatory process.

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