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Effect of herpes simplex virus vector-mediated interleukin-4 gene therapy on bladder overactivity and nociception

Gene Therapy volume 20, pages 194–200 (2013)Cite this article

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Abstract

We investigated the effects of replication-defective herpes simplex virus (HSV) vector expression of interleukin-4 (IL-4) on bladder overactivity and nociception. HSV vector expressing murine interleukin-4 (S4IL4) or the control vector expressing β-galactosidase (SHZ) were injected to the rat bladder wall. At 1 week after viral injection, in cystometry performed under urethane anesthesia, the S4IL4-treated group did not show the intercontraction intervals reduction during intravesical administration of 10 nM resiniferatoxin (RTx). At 2 weeks after viral injection, behavioral studies were performed on vector-injected animals in an awakened state. Freezing behavior induced by 3 μM RTx, administered for 1 min into the bladder, was significantly suppressed in the S4IL4 group compared with the SHZ group. Murine IL-4 levels examined by ELISA were significantly increased in bladder and bladder afferent dorsal root ganglia at 2 weeks after viral injection. The expression of IL-1β and IL-2 and bladder inflammatory responses were significantly suppressed in the RTx-irritated bladder of S4IL4-injected rats. These results indicate that HSV vector-mediated interleukin-4 expression in the bladder and bladder afferent pathways reduces the inflammatory response, bladder overactivity and nociceptive behavior induced by bladder irritation in the rat model. Therefore, IL-4 gene therapy could be a new strategy for treating urinary frequency and/or bladder pain.

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Acknowledgements

This study was supported by National Institutes of Health grants (DK057267, DK088836 and P01 DK044935) and the Samuel Wilan Research Fund for Interstitial Cystitis.

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Authors and Affiliations

  1. Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    T Oguchi, Y Funahashi, H Yokoyama & N Yoshimura

  2. Department of Urology, Shinshu University School of Medicine, Nagano, Japan

    T Oguchi, H Yokoyama & O Nishizawa

  3. Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    W F Goins, J R Goss & J C Glorioso

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  1. T Oguchi
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  2. Y Funahashi
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Correspondence to N Yoshimura.

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Oguchi, T., Funahashi, Y., Yokoyama, H. et al. Effect of herpes simplex virus vector-mediated interleukin-4 gene therapy on bladder overactivity and nociception. Gene Ther 20, 194–200 (2013). https://doi.org/10.1038/gt.2012.24

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