Bradykinin-induced blood–tumor barrier opening is mediated by tumor necrosis factor-α

Bradykinin has been shown to increase the permeability of blood–tumor barrier (BTB) selectively. This study was performed to determine whether tumor necrosis factor-α (TNF-α) was involved in the regulation of this biological process. We found that the levels of TNF-α mRNA and heat shock factor-1 (HSF1) protein in C6 cells were markedly up-regulated by bradykinin via real-time RT-PCR and Western blot methods. And the most obvious increase of HSF1 protein and TNF-α mRNA in C6 cells were observed at 5 min and 10 min of bradykinin perfusion, respectively. In addition, the radioactivity of TNF-α in C6 cells’ culture fluid also mostly increased at 15 min of bradykinin perfusion. And the Evans blue content of brain tumor tissues in rats and the concentration of TNF-α reached the maximum at 15 min of bradykinin perfusion. Our results suggested that the bradykinin-mediated BTB permeability increase is due to accelerated release of TNF-α, which could cause the increase of BTB permeability by promoting to the release HSF1 from neurospongioma cells.