Bladder Injury Model Induced in Rats by Exposure to Protamine Sulfate Followed by Bacterial Endotoxin

Stein, Paul C.; Pham, Hien; Ito, Takaaki; Parsons, C. Lowell

doi:10.1016/s0022-5347(01)66406-1

Cited by 61 publications

(32 citation statements)

References 11 publications

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“…Other investigators have demonstrated that TLR4-deficient C3H/HeJ mice exhibit a reduced inflammatory response to E. coli and exhibit significantly higher bacterial counts in the bladder and kidneys [31], [51], [52]. Although TLR4 is expressed on urinary epithelium, there is conflicting evidence about whether the epithelial cells respond to LPS [53], [54], [55], [56], [57]. We found that the murine bladder was highly responsive to in vivo injection of flagellin, but relatively unresponsive to highly purified LPS [30].…”

Section: Discussionmentioning

confidence: 99%

Toll-Like Receptor Polymorphisms and Susceptibility to Urinary Tract Infections in Adult Women

et al. 2009

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BackgroundAlthough behavioral risk factors are strongly associated with urinary tract infection (UTI) risk, the role of genetics in acquiring this disease is poorly understood.Methodology/Principal FindingsTo test the hypothesis that polymorphisms in Toll-like receptor (TLR) pathway genes are associated with susceptibility to UTIs, we conducted a population-based case-control study of women ages 18–49 years. We examined DNA variants in 9 TLR pathway genes in 431 recurrent cystitis (rUTI) cases, 400 pyelonephritis cases, and 430 controls with no history of UTIs. In the Caucasian subgroup of 987 women, polymorphism TLR4_A896G was associated with protection from rUTI, but not pyelonephritis, with an odds ratio (OR) of 0.54 and a 95% confidence interval (CI) of 0.31 to 0.96. Polymorphism TLR5_C1174T, which encodes a variant that abrogates flagellin-induced signaling, was associated with an increased risk of rUTI (OR(95%CI): 1.81 (1.00–3.08)), but not pyelonephritis. Polymorphism TLR1_G1805T was associated with protection from pyelonephritis (OR(95%CI): 0.53 (0.29–0.96)).ConclusionsThese results provide the first evidence of associations of TLR5 and TLR1 variants with altered risks of acquiring rUTI and pyelonephritis, respectively. Although these data suggest that TLR polymorphisms are associated with adult susceptibility to UTIs, the statistical significance was modest and will require further study including validation with independent cohorts.

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Section: Discussionmentioning

confidence: 99%

Toll-Like Receptor Polymorphisms and Susceptibility to Urinary Tract Infections in Adult Women

et al. 2009

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“…More recently, PS has been used in conjunction with bacterial induced cystitis. Instillation of both PS and E. coli lipopolysaccharide to, respectively, damage the urothelium and induce a visceral inflammatory cascade may help clarify the interaction(s) of multiple processes underlying LUT symptoms in BPS/IC [47, 60]. …”

Section: Bladder Pain Syndrome (Bps)/interstitial Cystitis (Ic)mentioning

confidence: 99%

The Role(s) of Cytokines/Chemokines in Urinary Bladder Inflammation and Dysfunction

Gonzalez

Arms

Vizzard

2014

BioMed Research International

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Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a chronic pain syndrome characterized by pain, pressure, or discomfort perceived to be bladder related and with at least one urinary symptom. It was recently concluded that 3.3–7.9 million women (>18 years old) in the United States exhibit BPS/IC symptoms. The impact of BPS/IC on quality of life is enormous and the economic burden is significant. Although the etiology and pathogenesis of BPS/IC are unknown, numerous theories including infection, inflammation, autoimmune disorder, toxic urinary agents, urothelial dysfunction, and neurogenic causes have been proposed. Altered visceral sensations from the urinary bladder (i.e., pain at low or moderate bladder filling) that accompany BPS/IC may be mediated by many factors including changes in the properties of peripheral bladder afferent pathways such that bladder afferent neurons respond in an exaggerated manner to normally innocuous stimuli (allodynia). The goals for this review are to describe chemokine/receptor (CXCL12/CXCR4; CCL2/CCR2) signaling and cytokine/receptor (transforming growth factor (TGF-β)/TGF-β type 1 receptor) signaling that may be valuable LUT targets for pharmacologic therapy to improve urinary bladder function and reduce somatic sensitivity associated with urinary bladder inflammation.

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“…Intravesicular instillation of LPS has been used to initiate biochemical and morphological cystitis in the mouse [19] and rat [12,20,21] and some degree of inflammasome activation has been reported, by us, using this technique [9]. …”

Section: Discussionmentioning

confidence: 99%

“…While uropathogens have evolved mechanisms to overcome this obstacle, our understanding has not progressed to the point where we can duplicate them experimentally with individual PAMPs. Other investigators have utilized pre-treatment with protamine sulfate to disrupt the GAG layer and allow better access of PAMPs to the underlying urothelial layer [12], but this step itself causes significant damage to the urothelium and elicits inflammation independent of the PAMPs [13]. Therefore, our injection technique allows us to experimentally expose the urothelial cells in vivo to specific antigens while minimizing damage to the urothelium.…”

Section: Introductionmentioning

confidence: 99%

The NACHT, LRR and PYD Domains-Containing protein 3 (NLRP3) Inflammasome Mediates Inflammation and Voiding Dysfunction in a Lipopolysaccharide-Induced Rat Model of Cystitis

Hughes

Kennis

Youssef

et al. 2016

J Clin Cell Immunol

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Objective NOD-like receptors (NLRs) sense sterile and non-sterile signals and form inflammasomes which trigger an inflammatory response through the activation of caspase-1 and release of IL-1β. Recently we have shown the presence of several NLRs in the bladder urothelia and demonstrated the importance of NLRP3 in bladder outlet obstruction and cyclophosphamide-induced cystitis, both models of sterile inflammation. In this study we explore a role for NLRP3 in mediating the response to LPS, a key antigen of uropathogenic bacteria. Method In order to bypass the protective glycosaminoglycan layer lining the urothelium, LPS was directly injected into the bladder wall of Sprague-Dawley rats. Glyburide (a NLRP3 inhibitor) or vehicle was administered orally prior to and after injection. Rats were analyzed 24 h later. Inflammasome activity (caspase-1 activity, IL-1β release) and inflammation (Evan’s Blue extravasation, bladder weight) were assessed, as was physiological bladder function (urodynamics). Results Injection of LPS stimulated inflammasome activation (caspase-1 activity) and the release of IL-1β into the urine which was prevented by glyburide. Likewise, LPS increased inflammation, (bladder weight and the extravasation of Evan’s blue dye), and this was reversed by glyburide. Functionally, animals injected with saline alone demonstrated decreased voiding volume as measured by urodynamics. In the presence of LPS, additional urinary dysfunction was evident with decreased voiding pressures and threshold pressures. The decrease in voiding pressure was blocked by glyburide but the decrease in threshold pressure was not, suggesting that LPS has significant effects mediated by inflammasome-dependent and -independent mechanisms. Conclusion Overall, the results demonstrate the potential importance of inflammasomes in bacterial cystitis as well as the ability of the bladder wall injection technique to isolate the in vivo effects of specific inflammasome ligands to the physiological changes associated with cystitis.

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Bladder Injury Model Induced in Rats by Exposure to Protamine Sulfate Followed by Bacterial Endotoxin

Abstract: This rat bladder injury model is useful for examining controversial issues regarding bladder wall structure-function alterations induced by inflammation and possibly important in the pathobiological mechanisms involved in some patients with interstitial cystitis.

Cited by 61 publications

References 11 publications

Toll-Like Receptor Polymorphisms and Susceptibility to Urinary Tract Infections in Adult Women

Toll-Like Receptor Polymorphisms and Susceptibility to Urinary Tract Infections in Adult Women

The Role(s) of Cytokines/Chemokines in Urinary Bladder Inflammation and Dysfunction

The NACHT, LRR and PYD Domains-Containing protein 3 (NLRP3) Inflammasome Mediates Inflammation and Voiding Dysfunction in a Lipopolysaccharide-Induced Rat Model of Cystitis

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