Bradykinin-induced blood-tumor barrier opening is mediated by tumor necrosis factor-alpha.
Bradykinin has been shown to increase the permeability of blood-tumor barrier (BTB) selectively. This study was performed to determine whether tumor necrosis factor-alpha (TNF-alpha) was involved in the regulation of this biological process. We found that the levels of TNF-alpha 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-alpha mRNA in C6 cells were observed at 5 min and 10 min of bradykinin perfusion, respectively. In addition, the radioactivity of TNF-alpha 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-alpha 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-alpha, which could cause the increase of BTB permeability by promoting to the release HSF1 from neurospongioma cells.
Qin
Li-Juan
LJ
Department of physiology, College of Basic Medical Sciences, Inner Mongolia Medical College, Huhehaote 010059, Inner Mongolia Municipality, PR China.
Gu
Yan-Ting
YT
Zhang
Hua
H
Xue
Yi-Xue
YX
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002199:Capillary Permeability / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D018835:Chaperonin 10 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013491:Suppressor Factors, Immunologic / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D018835:Chaperonin 10; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D013491:Suppressor Factors, Immunologic; D014409:Tumor Necrosis Factor-alpha; C025124:early pregnancy factor; D001920:Bradykinin