Nuclear factor-kappaB 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)-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.
Maiuri
Maria Chiara
MC
Dipartimento di Farmacologia Sperimentale, Scienze Biomorfologiche, and Biochimica e Biotecnologie Mediche, Federico II University of Naples, Via D. Montesano 49, 80131 Naples, Italy.
Tajana
Gianfranco
G
Iuvone
Teresa
T
De Stefano
Daniela
D
Mele
Guido
G
Ribecco
Maria Teresa
MT
Cinelli
Maria Pia
MP
Romano
Maria Fiammetta
MF
Turco
Maria Caterina
MC
Carnuccio
Rosa
R
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
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