Sub-noxious Intravesical Lipopolysaccharide Triggers Bladder Inflammation and Symptom Onset in A Transgenic Autoimmune Cystitis Model: A MAPP Network Animal Study

Paul Kogan; Suming Xu; Yaoqin Wang; Michael A O'Donnell; Susan K Lutgendorf; Catherine S Bradley; Andrew Schrepf; Karl J Kreder; Yi Luo

doi:10.1038/s41598-018-24833-x

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Sub-noxious Intravesical Lipopolysaccharide Triggers Bladder Inflammation and Symptom Onset in A Transgenic Autoimmune Cystitis Model: A MAPP Network Animal Study

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Sub-noxious Intravesical Lipopolysaccharide Triggers Bladder Inflammation and Symptom Onset in A Transgenic Autoimmune Cystitis Model: A MAPP Network Animal Study

Paul Kogan, Suming Xu, Yaoqin Wang, Michael A O'Donnell, Susan K Lutgendorf, Catherine S Bradley, Andrew Schrepf, Karl J Kreder and Yi Luo

Scientific reports, Vol.8(1), pp.6573-8

04/26/2018

DOI: 10.1038/s41598-018-24833-x

PMCID: PMC5919907

PMID: 29700406

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Abstract

Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) can potentially develop symptom flares after exposure to minor bladder irritants such as subclinical bacterial infection. To reproduce this symptom onset, we intravesically instilled a sub-noxious dose of uropathogenic E. coli component lipopolysaccharide (LPS) in young URO-OVA/OT-I mice, a transgenic autoimmune cystitis model that spontaneously develops bladder inflammation at ≥10 weeks of age. Female URO-OVA/OT-I mice (6-weeks old) were treated intravesically with phosphate-buffered saline (PBS) or PBS containing a sub-noxious dose (1 μg) of LPS. Mice were evaluated for bladder inflammation, pelvic pain, and voiding dysfunction at days 1, 7, and 14 post-treatment. Mice treated with LPS but not PBS developed early bladder inflammation with increased macrophage infiltration. Accordingly, the inflamed bladders expressed increased levels of mRNA for proinflammatory cytokines (IL-1β and IL-6) and pain mediator (substance P precursor). In addition, LPS-treated mice exhibited pelvic pain and voiding dysfunction such as increased urinary frequency and reduced bladder capacity. These functional changes sustained up to day 14 tested. Our results indicate that a single sub-noxious dose of intravesical LPS triggers early bladder inflammation and symptom onset in URO-OVA/OT-I mice, providing a useful model for IC/BPS symptom flare study.

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Title: Subtitle: Sub-noxious Intravesical Lipopolysaccharide Triggers Bladder Inflammation and Symptom Onset in A Transgenic Autoimmune Cystitis Model: A MAPP Network Animal Study
Creators: Paul Kogan - Department of Urology, University of Iowa, Iowa City, IA, USA
Suming Xu - Department of Urology, University of Iowa, Iowa City, IA, USA
Yaoqin Wang - Department of Urology, University of Iowa, Iowa City, IA, USA
Michael A O'Donnell - Department of Urology, University of Iowa, Iowa City, IA, USA
Susan K Lutgendorf - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA, USA
Catherine S Bradley - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA, USA
Andrew Schrepf - Department of Psychology, University of Iowa, Iowa City, IA, USA
Karl J Kreder - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA, USA
Yi Luo - Department of Urology, University of Iowa, Iowa City, IA, USA. yi-luo@uiowa.edu
Resource Type: Journal article
Publication Details: Scientific reports, Vol.8(1), pp.6573-8
DOI: 10.1038/s41598-018-24833-x
PMID: 29700406
PMCID: PMC5919907
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Publisher: England
Grant note: U01 DK082344 / NIDDK NIH HHS R01 DK100891 / NIDDK NIH HHS
Language: English
Date published: 04/26/2018
Academic Unit: Epidemiology; Psychological and Brain Sciences; Iowa Neuroscience Institute; Obstetrics and Gynecology; Urology
Record Identifier: 9983931815402771

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