Functional inhibition of NF-κB signal transduction in αvβ3 integrin expressing endothelial cells by using RGD-PEG-modified adenovirus with a mutant IκB gene

摘要: In order to selectively block nuclear factor κB (NF-κB)-dependent signal transduction in angiogenic endothelial cells, we constructed an αvβ3 integrin specific adenovirus encoding dominant negative IκB (dnIκB) as a therapeutic gene. By virtue of RGD modification the PEGylated virus, specificity cell entry pathway shifted from coxsacki-adenovirus receptor dependent entry. The outcome delivery transgene into cells was determined by analysis cellular responsiveness tumor necrosis (TNF)-α. Using real time reverse transcription PCR, mRNA levels adhesion molecules E-selectin, vascular molecule (VCAM)-1 and intercellular (ICAM)-1, cytokines/growth factors IL-6, IL-8 growth (VEGF)-A, tyrosine kinase Tie-2 were assessed. Furthermore, ICAM-1 protein flow cytometric analysis. RGD-targeted delivered dnIκB via become functionally expressed, leading complete abolishment TNF-α-induced up-regulation ICAM-1, VCAM-1, IL-8, VEGF-A Tie-2. approach targeted presented here can be employed for diseases such rheumatoid arthritis inflammatory bowel disease where activation NF-κB activity should locally restored basal endothelium.