Journal of Molecular Medicine

, Volume 87, Issue 5, pp 481–492 | Cite as

NF-κB blockade upregulates Bax, TSP-1, and TSP-2 expression in rat granulation tissue

  • Daniela De Stefano
  • Giancarlo Nicolaus
  • Maria Chiara Maiuri
  • Daniela Cipolletta
  • Lorenzo Galluzzi
  • Maria Pia Cinelli
  • Gianfranco Tajana
  • Teresa Iuvone
  • Rosa CarnuccioEmail author
Original Article


Several diseases are characterized by chronic inflammation, a condition frequently associated with angiogenesis and fibrogenesis that account for the development of granulation tissue. Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a crucial modulator of intracellular prosurvival signaling pathways and is implicated in the pathogenesis of inflammatory process. In this study, we have investigated the role of NF-κB in the angiogenic and fibrogenic response induced by λ-carrageenin in a rat model of chronic inflammation at 1, 3, and 5 days. The subcutaneous implant of λ-carrageenin-soaked sponges in rat induced a time-related increase of granulation tissue formation accompanied by intense neovascularization. These λ-carrageenin-induced changes were significantly reduced by coinjection of wild-type oligodeoxynucleotide (WT ODN) decoy to NF-κB. Molecular, morphological, and ultrastructural analysis performed on whole granulation tissue demonstrated: (1) inhibition of NF-κB/DNA binding activity; (2) downregulation of cyclooxygenase-2, matrix metalloproteinase-9, tumor necrosis factor-α, and vascular endothelial growth factor; (3) upregulation of thrombospondin (TSP)-1 at 1 day and TSP-2 at 5 days; and (4) increase in Bax to Bcl-2 ratio. Our findings show that the blockade of NF-κB activation by WT ODN decoy prevents the development of granulation tissue induced by λ-carrageenin-soaked sponge implant upregulating Bax as well as TSP-1 and TSP-2 expression.


Angiogenesis Apoptosis Bcl-2 protein family Granulation tissue NF-κB Phagocytosis 



Prof. M.L. Del Basso De Caro is gratefully thanked for the assistance and technical support. We also kindly acknowledge Dr. M.T. Ribecco for her constant help and invaluable suggestions. This work has been supported by the Italian Government.

Supplementary material

109_2009_443_MOESM1_ESM.doc (22 kb)
Supplementry legend information (DOC 22KB).
109_2009_443_MOESM2_ESM.ppt (1.7 mb)
Supplementry figures (PPT 1.71 MB).


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Daniela De Stefano
    • 1
  • Giancarlo Nicolaus
    • 2
  • Maria Chiara Maiuri
    • 1
  • Daniela Cipolletta
    • 2
  • Lorenzo Galluzzi
    • 3
  • Maria Pia Cinelli
    • 4
  • Gianfranco Tajana
    • 5
  • Teresa Iuvone
    • 6
  • Rosa Carnuccio
    • 1
    Email author
  1. 1.Dipartimento di Farmacologia Sperimentale, Facoltà di Scienze BiotecnologicheUniversità degli Studi di Napoli Federico IINaplesItaly
  2. 2.Istituto di Ricerche di Biologia Molecolare P. AngelettiPomeziaItaly
  3. 3.INSERM U848, Institut Gustave RoussyVillejuifFrance
  4. 4.Dipartimento di Scienze Biomorfologiche e Funzionali, Facoltà di Medicina e ChirurgiaUniversità degli Studi di Napoli Federico IINaplesItaly
  5. 5.Dipartimento di Scienze Farmaceutiche, Facoltà di Medicina e ChirurgiaUniversità degli Studi di SalernoFiscianoItaly
  6. 6.Dipartimento di Farmacologia Sperimentale, Facoltà di FarmaciaUniversità degli Studi di Napoli Federico IINaplesItaly

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