NF-κB blockade upregulates Bax, TSP-1, and TSP-2 expression in rat granulation tissue
Autor: | Maria Pia Cinelli, Teresa Iuvone, Rosa Carnuccio, Daniela De Stefano, Daniela Cipolletta, Gianfranco Tajana, Lorenzo Galluzzi, Maria Chiara Maiuri, Giancarlo Nicolaus |
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Přispěvatelé: | De Stefano, D., Nicolaus, G., Maiuri, MARIA CHIARA, Cipolletta, D., Galluzzi, L., Cinelli, M. P., Tajana, G., Iuvone, T., Carnuccio, R. |
Rok vydání: | 2009 |
Předmět: |
Male
Vascular Endothelial Growth Factor A Pathology medicine.medical_specialty Angiogenesis Blotting Western Electrophoretic Mobility Shift Assay Inflammation Biology Carrageenan Thrombospondin 1 Neovascularization chemistry.chemical_compound Microscopy Electron Transmission Downregulation and upregulation Drug Discovery medicine Animals NF-kappaB Rats Wistar Genetics (clinical) bcl-2-Associated X Protein Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha NF-kappa B Granulation tissue NF-κB Fibroblasts Immunohistochemistry Rats Up-Regulation Vascular endothelial growth factor medicine.anatomical_structure Matrix Metalloproteinase 9 Proto-Oncogene Proteins c-bcl-2 TSP-1/2 chemistry Cyclooxygenase 2 inflammation Bax Microscopy Electron Scanning Cancer research Molecular Medicine Tumor necrosis factor alpha medicine.symptom Oligonucleotide Probes Thrombospondins Protein Binding |
Zdroj: | Journal of Molecular Medicine. 87:481-492 |
ISSN: | 1432-1440 0946-2716 |
Popis: | 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-kappaB) 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-kappaB in the angiogenic and fibrogenic response induced by lambda-carrageenin in a rat model of chronic inflammation at 1, 3, and 5 days. The subcutaneous implant of lambda-carrageenin-soaked sponges in rat induced a time-related increase of granulation tissue formation accompanied by intense neovascularization. These lambda-carrageenin-induced changes were significantly reduced by coinjection of wild-type oligodeoxynucleotide (WT ODN) decoy to NF-kappaB. Molecular, morphological, and ultrastructural analysis performed on whole granulation tissue demonstrated: (1) inhibition of NF-kappaB/DNA binding activity; (2) downregulation of cyclooxygenase-2, matrix metalloproteinase-9, tumor necrosis factor-alpha, 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-kappaB activation by WT ODN decoy prevents the development of granulation tissue induced by lambda-carrageenin-soaked sponge implant upregulating Bax as well as TSP-1 and TSP-2 expression. |
Databáze: | OpenAIRE |
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