The study on the function and cell source of interleukin‐6 in interstitial cystitis/bladder painful syndrome rat model

Zheng, Zhaoqiang; Zhang, Jiapeng; Zhang, Caixia; Li, Wenshuang; Ma, Kaiqun; Huang, Hao; Li, Kuiqing; Yao, Yousheng

doi:10.1002/iid3.505

Cited by 8 publications

(2 citation statements)

References 21 publications

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“…Further, lower urine levels of IL-6 may re ect lower severity of symptoms. In a recent study, the FDAapproved drug tocilizumab that binds IL-6 was shown to reduce bladder in ammation in a rat model, supporting the potential repurposing of tocilizumab for IC/BPS (43). Such mechanistic clinical trials have the added bene t of shedding light on the mystery of how temporally brief urinary elevation of IL-6 is able to mediate chronic in ammation associated with IC/BPS (9,10,25,27).…”

Section: Discussionmentioning

confidence: 94%

Temporally complex inflammatory networks in an animal model reveal signatures for interstitial cystitis and bladder pain syndrome phenotype

Shah,

Vodovotz,

Yoshimura

et al. 2023

Neurourology and Urodynamics

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Introduction and ObjectiveInterstitial cystitis and bladder pain syndrome (IC/BPS) presents with symptoms of debilitating bladder pain and is typically a diagnosis of exclusion. The cystoscopic detection of Hunner's lesions increases the likelihood of detecting tissue inflammation on bladder biopsy and increases the odds of therapeutic success with anti‐inflammatory drugs. However, the identification of this subgroup remains challenging with the current lack of surrogate biomarkers of IC/BPS. On the path towards identifying biomarkers of IC/BPS, we modeled the dynamic evolution of inflammation in an experimental IC/BPS rodent model using computational biological network analysis of inflammatory mediators (cytokines and chemokines) released into urine. The use of biological network analysis allows us to identify urinary proteins that could be drivers of inflammation and could therefore serve as therapeutic targets for the treatment of IC/BPS.MethodsRats subjected to cyclophosphamide (CYP) injection (150 mg/kg) were used as an experimental model for acute IC/BPS (n = 8). Urine from each void was collected from the rats over a 12‐h period and was assayed for 13 inflammatory mediators using Luminex™. Time‐interval principal component analysis (TI‐PCA) and dynamic network analysis (DyNA), two biological network algorithms, were used to identify biomarkers of inflammation characteristic of IC/BPS over time.ResultsCompared to vehicle‐treated rats, nearly all inflammatory mediators were elevated significantly (p < 0.05) in the urine of CYP treated rats. TI‐PCA highlighted that GRO‐KC, IL‐5, IL‐18, and MCP‐1 account for the greatest variance in the inflammatory response. At early time points, DyNA indicated a positive correlation between IL‐4 and IL‐1β and between TNF‐α and IL‐1β. Analysis of TI‐PCA and DyNA at later time points showed the emergence of IL‐5, IL‐6, and IFNγ as additional key mediators of inflammation. Furthermore, DyNA network complexity rose and fell before peaking at 9.5 h following CYP treatment. This pattern of inflammation may mimic the fluctuating severity of inflammation associated with IC/BPS flares.ConclusionsComputational analysis of inflammation networks in experimental IC/BPS analysis expands on the previously accepted inflammatory signatures of IC by adding IL‐5, IL‐18, and MCP‐1 to the prior studies implicating IL‐6 and GRO as IC/BPS biomarkers. This analysis supports a complex evolution of inflammatory networks suggestive of the rise and fall of inflammation characteristic of IC/BPS flares.

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Section: Discussionmentioning

confidence: 94%

Temporally complex inflammatory networks in an animal model reveal signatures for interstitial cystitis and bladder pain syndrome phenotype

Shah,

Vodovotz,

Yoshimura

et al. 2023

Neurourology and Urodynamics

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“…In addition, stimulating bladder epithelial cells with IL1β induces the expression and release of IL6. Thus, IL6 is produced in the bladder epithelial and stromal layers [ 7 ] and is thought to play a role in cystitis development [ 25 ]. Indeed, it has been reported that urinary IL6 levels are higher in patients with IC than in healthy individuals [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

Rosmarinic acid ameliorates HCl-induced cystitis in rats

Kitamura

Yamamoto

et al. 2023

PLoS ONE

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Shiso (Perilla frutescens var crispa f. purprea) is a traditional medicinal herb that exerts anti-inflammatory effects and alleviates lower urinary tract symptoms. In this study, we examined the effects of rosmarinic acid, a major polyphenol in shiso, on urinary function and the bladder in a rat hydrochloric acid-induced cystitis model. Sprague–Dawley rats were administered intravesically with hydrochloric acid or saline solution (control) to induce cystitis. Afterwards, the rats were administered orally with distilled water or rosmarinic acid for three days and then the intravesical pressure was measured, a stretch stimulation test was performed using the harvested bladder, and histological and biochemical analyses were performed. In addition, we investigated the effects of rosmarinic acid on the expression of inflammation-related molecules in normal human bladder epithelial cells. Rosmarinic acid ameliorated hydrochloric acid-induced shortening of micturition interval by 49%. In hydrochloric acid-treated bladders, significantly more prostaglandin E2 was released after stretching; however, rosmarinic acid suppressed its release to control levels. Rosmarinic acid also reduced hydrochloric acid-induced epithelial thickening and the levels of inflammatory molecules in the bladder. Furthermore, rosmarinic acid suppressed interleukin 1β-induced increases in Cox2 and Il6 expression in bladder epithelial cells. These findings indicate that rosmarinic acid can ameliorate hydrochloric acid-induced cystitis in rats and that these effects are due, at least in part, to its anti-inflammatory effects on the bladder and inhibition of stretch-induced prostaglandin E2 release.

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Hispidulin targets PTGS2 to improve cyclophosphamide-induced cystitis by suppressing NLRP3 inflammasome

Liu,

Li,

Dong

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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The study on the function and cell source of interleukin‐6 in interstitial cystitis/bladder painful syndrome rat model

Cited by 8 publications

References 21 publications

Temporally complex inflammatory networks in an animal model reveal signatures for interstitial cystitis and bladder pain syndrome phenotype

Temporally complex inflammatory networks in an animal model reveal signatures for interstitial cystitis and bladder pain syndrome phenotype

Rosmarinic acid ameliorates HCl-induced cystitis in rats

Hispidulin targets PTGS2 to improve cyclophosphamide-induced cystitis by suppressing NLRP3 inflammasome

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