Urothelial lesion formation is mediated by TNFR1 during neurogenic cystitis

American Journal of Physiology. Renal Physiology
Michael C ChenDavid J Klumpp

Abstract

Interstitial cystitis (IC) is a chronic bladder inflammatory disease of unknown etiology that shares similarities with Crohn's disease and psoriasis. IC, often regarded as a neurogenic cystitis, is associated with urothelial lesions that likely compromise the bladder permeability barrier and thereby contribute to patient morbidity. Here, we use a murine model of neurogenic cystitis to investigate the mechanism of urothelial lesion formation and find that urothelial apoptosis induces formation of lesions. Lesions formed in wild-type mice but not in mice deficient in TNF, TNF receptors, or mast cells. In urothelial cultures, only siRNAs targeting TNFR1, but not TNFR2, blocked TNF-induced apoptosis, indicating a primary role for TNFR1. Trans-epithelial resistance, a measure of bladder barrier function, decreased during neurogenic cystitis in wild-type and TNFR2(-/-) mice but was stabilized in TNF(-/-) mice. Anti-TNF antibodies both altered bladder mast cell localization and stabilized barrier function. Based on these findings, we conclude that mast cell activation and release of TNF drive urothelial apoptosis and lesion formation in a murine neurogenic cystitis model, and we hypothesize that anti-TNF therapy may stabilize bladder ...Continue Reading

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Citations

Dec 31, 2010·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Zun-Yi Wang, Dale E Bjorling
Nov 26, 2010·Current Allergy and Asthma Reports·Craig Smuda, Paul J Bryce
Jun 1, 2012·American Journal of Physiology. Renal Physiology·Wenbin YangDavid J Klumpp
Nov 17, 2009·BMC Urology·Charles N RudickDavid J Klumpp
May 8, 2008·PloS One·Charles N RudickDavid J Klumpp
May 5, 2009·PLoS Pathogens·Praveen ThumbikatDavid J Klumpp
Nov 6, 2015·International Journal of Molecular Sciences·Min-Kyung JangMyeong Ho Jung
Dec 20, 2011·The Journal of Urology·Charles N RudickDavid J Klumpp
Dec 23, 2015·International Journal of Molecular Sciences·Anupam AichKalpna Gupta
Sep 5, 2008·Nature Clinical Practice. Urology·David J Klumpp, Charles N Rudick
Nov 10, 2017·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Wenbin YangDavid J Klumpp
Mar 20, 2020·Physiological Reviews·Marianela G DalghiGerard Apodaca
Feb 5, 2021·Trends in Immunology·Jianxuan Wu, Soman N Abraham

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