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

Published

Journal Article

AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The NLRP3/IL-1β-mediated inflammation pathway plays a significant role in denervation during BOO.

Full Text

Duke Authors

Cited Authors

  • Lütolf, R; Hughes, FM; Inouye, BM; Jin, H; McMains, JC; Pak, ES; Hannan, JL; Purves, JT

Published Date

  • March 2018

Published In

Volume / Issue

  • 37 / 3

Start / End Page

  • 952 - 959

PubMed ID

  • 28984997

Pubmed Central ID

  • 28984997

Electronic International Standard Serial Number (EISSN)

  • 1520-6777

Digital Object Identifier (DOI)

  • 10.1002/nau.23419

Language

  • eng

Conference Location

  • United States