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
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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