NLRP3/IL-1β mediates denervation during bladder outlet obstruction in rats.
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 articleSubject
NLRP3benign prostatic hyperplasia
bladder outlet obstruction
cytokines
glyburide
inflammasomes
interleukin
interleukin-1 receptor antagonist
interleukin-1beta
neuron
neuroscience
urinary bladder
urology
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https://hdl.handle.net/10161/17172Published Version (Please cite this version)
10.1002/nau.23419Publication 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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Show full item recordScholars@Duke
Monty Hughes Jr.
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 l
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.
J Todd Purves
Professor of Urology
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