title: Nuclear factor-kappaB regulates inflammatory cell apoptosis and phagocytosis in rat carrageenin-sponge implant model.
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.
authors.affiliation: Dipartimento di Farmacologia Sperimentale, Scienze Biomorfologiche, and Biochimica e Biotecnologie Mediche, Federico II University of Naples, Via D. Montesano 49, 80131 Naples, Italy.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Maiuri
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Tajana
authors.forename: Teresa
authors.initials: T
authors.lastname: Iuvone
authors.forename: Daniela
authors.initials: D
authors.lastname: De Stefano
authors.forename: Guido
authors.initials: G
authors.lastname: Mele
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Ribecco
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Cinelli
authors.forename: Maria Fiammetta
authors.initials: MF
authors.lastname: Romano
authors.forename: Maria Caterina
authors.initials: MC
authors.lastname: Turco
authors.forename: Rosa
authors.initials: R
authors.lastname: Carnuccio
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002351:Carrageenan / Q000633:toxicity*; D002465:Cell Movement; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009566:Nitrates / Q000032:analysis; D009573:Nitrites / Q000032:analysis; D009841:Oligonucleotides / Q000627:therapeutic use; D010587:Phagocytosis / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014157:Transcription Factors / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000032:analysis; D053773:Transforming Growth Factor beta1
chemical_list: D016328:NF-kappa B; D009566:Nitrates; D009573:Nitrites; D009841:Oligonucleotides; C508962:Tgfb1 protein, rat; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D002351:Carrageenan