| Autor: |
De Stefano, Daniela, Nicolaus, Giancarlo, Maiuri, Maria, Cipolletta, Daniela, Galluzzi, Lorenzo, Cinelli, Maria Pia, Tajana, Gianfranco, Iuvone, Teresa, Carnuccio, Rosa |
| Předmět: |
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| Zdroj: |
Journal of Molecular Medicine; May2009, Vol. 87 Issue 5, p481-492, 12p, 1 Color Photograph, 1 Black and White Photograph, 1 Diagram, 4 Graphs |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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