Herpes simplex virus vector mediated gene therapy of tumor necrosis factor-α blockade for bladder overactivity and nociception in rats.
J Urol
; 189(1): 366-73, 2013 Jan.
Article
em En
| MEDLINE
| ID: mdl-23174234
ABSTRACT
PURPOSE:
We examined the effects of tumor necrosis factor-α blockade on bladder overactivity and nociception using replication defective HSV vectors expressing tumor necrosis factor-α soluble receptor. MATERIALS ANDMETHODS:
HSV vectors expressing tumor necrosis factor-α soluble receptor or ß-galactosidase/green fluorescent protein as the control were injected into the bladder wall of female Sprague-Dawley® rats. Green fluorescent protein was observed with fluorescent microscopy in the bladder and L6 dorsal root ganglia. mRNA and protein expression of tumor necrosis factor-α, and interleukin-1ß and 6 as well as myeloperoxidase activity in the bladder were determined by quantitative reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay 4 hours after intravesical resiniferatoxin administration. c-Fos positive neurons were counted in the L6 spinal dorsal horn. Cystometry and behavioral analyses were also performed.RESULTS:
Green fluorescent protein expression was confirmed in the bladder and L6 dorsal root ganglia. Resiniferatoxin administration significantly increased tumor necrosis factor-α mRNA and protein levels in the bladder in controls. Tumor necrosis factor-α mRNA was also increased in the tumor necrosis factor-α soluble receptor group, although tumor necrosis factor-α protein up-regulation was suppressed. The up-regulation of interleukin-1ß and 6 mRNA and protein levels, and the myeloperoxidase activity seen in controls were suppressed in the tumor necrosis factor-α soluble receptor group. c-Fos positive cells in the L6 spinal dorsal horn were less prominent in the tumor necrosis factor-α soluble receptor group than in controls. On cystometry the significant decrease in intercontraction intervals after resiniferatoxin infusion detected in controls was not seen in the tumor necrosis factor-α soluble receptor group. On behavioral analyses freezing behavior was significantly decreased in the tumor necrosis factor-α soluble receptor group without affecting licking behavior.CONCLUSIONS:
HSV vector mediated tumor necrosis factor-α blockade gene therapy in the bladder and bladder afferent pathways decreases the bladder pain and overactivity induced by nociceptive bladder stimuli.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Terapia Genética
/
Fator de Necrose Tumoral alfa
/
Simplexvirus
/
Bexiga Urinária Hiperativa
/
Nociceptividade
Limite:
Animals
Idioma:
En
Revista:
J Urol
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos