Bladder fibrosis during outlet obstruction is triggered through the NLRP3 inflammasome and the production of IL-1 β.

Bladder fibrosis during outlet obstruction is triggered through the NLRP3 inflammasome and the production of IL-1β.
Am J Physiol Renal Physiol. 2017 Jun 07;:ajprenal.00128.2017
Authors: Hughes FM, Sexton SJ, Jin H, Govada V, Purves JT
Abstract
Bladder outlet obstruction (BOO) triggers inflammation in the bladder through the NLRP3 inflammasome. BOO also activates fibrosis, which is largely responsible for the decompensation of the bladder in the chronic state. Because fibrosis can be driven by inflammation, we have explored a role for NLRP3 (and IL-1β produced by NLRP3) in the activation and progression of BOO-induced fibrosis. Female rats were divided into 5 groups: 1) control, 2) sham, 3) BOO + Vehicle, 4) BOO + the NLRP3 inhibitor glyburide or 5) BOO + the IL-1β receptor antagonist anakinra. Fibrosis was assessed by Masson's Trichrome Stain, collagen secretion via Sirius Red, and protein localization by immunofluorescence. BOO increased collagen production in the bladder which was blocked by glyburide and anakinra, clearly implicating the NLRP3/IL-1β pathway in fibrosis. The collagen was primarily found in the lamina propria and the smooth muscle, while IL-1 receptor 1 and prolyl 4-hydroylase (an enzyme involved in the intracellular modification of collagen) both localized to the urothelium and the smooth muscle. Lysyl oxidase, the enzyme involved in the final extracellular assembly of mature collagen fibrils, was found to some...

Source: American Journal of Physiology. Renal Physiology - June 7, 2017 Category: Physiology Authors: Hughes FM, Sexton SJ, Jin H, Govada V, Purves JT Tags: Am J Physiol Renal Physiol Source Type: research