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

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Abstract

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.

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Acknowledgements

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.

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Authors and Affiliations

  1. Dipartimento di Farmacologia Sperimentale, Facoltà di Scienze Biotecnologiche, Università degli Studi di Napoli Federico II, Via D. Montesano, 49, 80131, Naples, Italy

    Daniela De Stefano, Maria Chiara Maiuri & Rosa Carnuccio

  2. Istituto di Ricerche di Biologia Molecolare P. Angeletti, 00040, Pomezia, Italy

    Giancarlo Nicolaus & Daniela Cipolletta

  3. INSERM U848, Institut Gustave Roussy, 94805, Villejuif, France

    Lorenzo Galluzzi

  4. Dipartimento di Scienze Biomorfologiche e Funzionali, Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli Federico II, 80131, Naples, Italy

    Maria Pia Cinelli

  5. Dipartimento di Scienze Farmaceutiche, Facoltà di Medicina e Chirurgia, Università degli Studi di Salerno, 84084, Fisciano, Salermo, Italy

    Gianfranco Tajana

  6. Dipartimento di Farmacologia Sperimentale, Facoltà di Farmacia, Università degli Studi di Napoli Federico II, 80131, Naples, Italy

    Teresa Iuvone

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  1. Daniela De Stefano
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  2. Giancarlo Nicolaus
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  9. Rosa Carnuccio
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Correspondence to Rosa Carnuccio.

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De Stefano, D., Nicolaus, G., Maiuri, M.C. et al. NF-κB blockade upregulates Bax, TSP-1, and TSP-2 expression in rat granulation tissue. J Mol Med 87, 481–492 (2009). https://doi.org/10.1007/s00109-009-0443-6

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  • DOI: https://doi.org/10.1007/s00109-009-0443-6

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