NLRP3/IL-1β mediates denervation during bladder outlet obstruction in rats.


Denervation of the bladder is a detrimental consequence of bladder outlet obstruction (BOO). We have previously shown that, during BOO, inflammation triggered by the NLRP3 inflammasome in the urothelia mediates physiological bladder dysfunction and downstream fibrosis in rats. The aim of this study was to assess the effect of NLRP3-mediated inflammation on bladder denervation during BOO.There were five groups of rats: (i) Control (no surgery); (ii) Sham-operated; (iii) BOO rats given vehicle; (iv) BOO rats given the NLRP3 inhibitor glyburide; and (v) BOO rats given the IL-1 receptor antagonist anakinra. BOO was constructed by ligating the urethra over a 1 mm catheter and removing the catheter. Medications were given prior to surgery and once daily for 12 days. Bladder sections were stained for PGP9.5, a pan-neuronal marker. Whole transverse sections were used to identify and count nerves while assessing cross-sectional area. For in vitro studies, pelvic ganglion neurons were isolated and treated with IL-1β. After a 48 h incubation apoptosis, neurite length and branching were assessed.In obstructed bladders, the number of nerves decreased while total area increased, indicating a loss of cell number and/or branching. The decrease in nerve density was blocked by glyburide or anakinra, clearly implicating the NLRP3 pathway in denervation. In vitro analysis demonstrated that IL-1β, a product of the inflammasome, induced apoptosis in pelvic ganglion neurons, suggesting one mechanism of BOO-induced denervation is NLRP3/IL-1β triggered apoptosis.The NLRP3/IL-1β-mediated inflammation pathway plays a significant role in denervation during BOO.





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Publication Info

Lütolf, Robin, Francis M Hughes, Brian M Inouye, Huixia Jin, Jennifer C McMains, Elena S Pak, Johanna L Hannan, J Todd Purves, et al. (2018). NLRP3/IL-1β mediates denervation during bladder outlet obstruction in rats. Neurourology and urodynamics, 37(3). pp. 952–959. 10.1002/nau.23419 Retrieved from

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Monty Hughes

Assistant Professor in Urology

 Dr. Hughes received his Ph.D. from the Medical University of South Carolina and was a post doc at both the University of North Carolina at Chapel Hill and NIH. He then joined the faculty of the University of North Carolina at Charlotte where he rose to the rank of Associate Professor (with tenure). Following a brief stint as the director of the biology division of a start-up pharmaceutical company, he joined forces with Dr. Purves at the Medical University of South Carolina to begin this lab focused on benign urinary disorders. Dr. Hughes has been at Duke since 2015. He is currently an Assistant Professor working within the Department of Surgery and Division of Urology. He serves as the Director of the Urinary Dysfunction Laboratory which studies the role of inflammation in disorders such as bladder outlet obstruction and diabetic bladder dysfunction. In association with Dr. J Todd Purves, this lab has been instrumental in demonstrating the central importance of the NLRP3 inflammasome in sensing the biochemical stressors associated with these disorders and translating them into an inflammatory signal. This signal is ultimately responsible for changes in voiding function, denervation and fibrosis.


J Todd Purves

Professor of Urology

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