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

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Date
2018-03
Authors
Lütolf, Robin
Hughes, Francis M
Inouye, Brian M
Jin, Huixia
McMains, Jennifer C
Pak, Elena S
Hannan, Johanna L
Purves, J Todd
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Abstract
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.
Type
Journal article
Subject
NLRP3
benign prostatic hyperplasia
bladder outlet obstruction
cytokines
glyburide
inflammasomes
interleukin
interleukin-1 receptor antagonist
interleukin-1beta
neuron
neuroscience
urinary bladder
urology
Permalink
https://hdl.handle.net/10161/17172
Published Version (Please cite this version)
10.1002/nau.23419
Publication Info
Lütolf, Robin; Hughes, Francis M; Inouye, Brian M; Jin, Huixia; McMains, Jennifer C; Pak, Elena S; ... Purves, J Todd (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 https://hdl.handle.net/10161/17172.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Hughes

Monty Hughes Jr.

Assistant Professor in Surgery
 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 l
Inouye

Brian Masao Inouye

Clinical Associate in the Department of Surgery
This author no longer has a Scholars@Duke profile, so the information shown here reflects their Duke status at the time this item was deposited.
Purves

J Todd Purves

Associate Professor of Surgery
Alphabetical list of authors with Scholars@Duke profiles.
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