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

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-lightchain- 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 wildtype 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.