Treatment with low-energy shock wave alleviates pain in an animal model of uroplakin 3A-induced autoimmune interstitial cystitis/painful bladder syndrome

Li, Huixi; Zhang, Zhichao; Peng, Jing; Xin, Zhongcheng; Li, Meng; Yang, Bicheng; Fang, Dong; Tang, Yuan; Guo, Yinglu

doi:10.4111/icu.2019.60.5.359

Cited by 14 publications

(12 citation statements)

References 28 publications

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“…Enzyme-linked immunosorbent assays (ELISA). For muTNF-α quantitation by ELISA, serum and PBS brain homogenates were diluted with the ELISA sample buffer and sample duplicates were run on specific sandwich colorimetric ELISAs (Biolegend) according to the manufacturer's protocol as previously described 64 . Optical (2020) 10:8670 | https://doi.org/10.1038/s41598-020-65378-2 www.nature.com/scientificreports www.nature.com/scientificreports/ densities at 450 nm of each well were read on a microplate reader (ELx800, BioTek Instruments, Winooski, VT, USA), and sample TNF-α concentrations were determined by comparison with the respective standard curves using the Gen5 software (BioTek Instruments).…”

Section: Methodsmentioning

confidence: 99%

A 3′UTR modification of the TNF-α mouse gene increases peripheral TNF-α and modulates the Alzheimer-like phenotype in 5XFAD mice

Kalovyrna

Apokotou

Boulekou

et al. 2020

Sci Rep

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Tumor necrosis factor-α (TNF-α) is a pro-inflammatory cytokine, involved in Alzheimer's disease pathogenesis. Anti-TNF-α therapeutic approaches currently used in autoimmune diseases have been proposed as a therapeutic strategy in AD. We have previously examined the role of TNF-α and anti-TNF-α drugs in AD, using 5XFAD mice, and we have found a significant role for peripheral TNF-α in brain inflammation. Here we investigated the role of mouse TNF-α on the AD-like phenotype of 5XFAD mice using a knock-in mouse with deletion of the 3'UTR of the endogenous TNF-α (tnf ΔARe/+) that develops rheumatoid arthritis and Crohn's disease. 5XFAD/TNF ΔARe/+ mice showed significantly decreased amyloid deposition. Interestingly, microglia but not astrocytes were activated in 5XFAD/ tnf ΔARe/+ brains. This microglial activation was associated with increased infiltrating peripheral leukocytes and perivascular macrophages and synaptic degeneration. APP levels and APP processing enzymes involved in Aβ production remained unchanged, suggesting that the reduced amyloid burden can be attributed to the increased microglial and perivascular macrophage activation caused by TNFα. Peripheral TNF-α levels were increased while brain TNF-α remained the same. These data provide further evidence for peripheral TNF-α as a mediator of inflammation between the periphery and the brain. Alzheimer's disease (AD) is the most common cause of dementia among the elderly characterized by severe memory loss and cognitive impairment 1. Although beta-amyloid (Αβ) is traditionally accepted as the main initiator of the disease, numerous failed clinical trials targeting Αβ 2 have changed research focus on other factors involved in the disease as brain inflammation, commonly called neuroinflammation 3,4. Moreover, clinical and experimental studies have provided significant evidence that peripheral inflammation may be associated with increased neuroinflammation and accelerated AD progression. A number of pro-inflammatory molecules including TNF-α, have been implicated in AD pathogenetic process 5. TNF-α has been shown to colocalize with amyloid plaques in AD human brains and animal models 6,7 and elevated TNF-α levels have been detected in the serum and cerebrospinal fluid (CSF) of AD patients 6,8,9. TNF-α is a pleiotropic pro-inflammatory cytokine that mediates its effect through two different receptors, TNF-α receptor I (p55) and TNF-α receptor II (p75) 10. TNF-α central role in the pathogenesis of chronic autoimmune diseases like rheumatoid arthritis (RA), psoriasis and Crohn's disease 11-14 has led to the development of anti-TNF-α therapeutics widely used in the treatment of autoimmune diseases 15,16. Case studies have reported that treatment of AD patients with the anti-TNF-α agents currently used in RA or Crohn's disease, was beneficial and improved cognitive impairment 17-19 while epidemiological studies showed that AD risk is reduced in RA patients receiving anti-TNF-α agents 20. We have previously shown that peripheral human TNF-α and anti-TNF-α therapy, c...

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Section: Methodsmentioning

confidence: 99%

A 3′UTR modification of the TNF-α mouse gene increases peripheral TNF-α and modulates the Alzheimer-like phenotype in 5XFAD mice

Kalovyrna

Apokotou

Boulekou

et al. 2020

Sci Rep

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“…Recently, Li et al. reported that local treatment with low‐energy shock wave improved bladder inflammation and pain, and reduced levels of TNF‐α and NGF in bladder and serum in the EAC mice 119 …”

Section: Animal Modelsmentioning

confidence: 99%

Interstitial cystitis/bladder pain syndrome: The evolving landscape, animal models and future perspectives

et al. 2020

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Abbreviations & Acronyms BPS = bladder pain syndrome CCL2 = C-C motif ligand 2 CNS = central nervous system DMSO = dimethyl sulfoxide EAC = experimental autoimmune cystitis ESSIC = International Society for the Study of BPS FSS = functional somatic syndrome GAG = glycosaminoglycan IC = interstitial cystitis IFN-c = interferon-gamma IL = interleukin MC = mast cell NGF = nerve growth factor OVA = ovalbumin TCR = T-cell receptor TNF = tumor necrosis factor TLR = Toll-like receptor UCPPS = urological chronic pelvic pain syndrome UPK = uroplakin Upo = unpublished observation VEGF = vascular endothelial growth factor WAS = water avoidance stress Correspondence: Yoshiyuki Abstract: Interstitial cystitis/bladder pain syndrome is a debilitating condition of unknown etiology characterized by persistent pelvic pain with lower urinary tract symptoms and comprises a wide variety of potentially clinically useful phenotypes with different possible etiologies. Current clinicopathological and genomic evidence suggests that interstitial cystitis/bladder pain syndrome should be categorized by the presence or absence of Hunner lesions, rather than by clinical phenotyping based on symptomatology. The Hunner lesion subtype is a distinct inflammatory disease with proven bladder etiology characterized by epithelial denudation and enhanced immune responses frequently accompanied by clonal expansion of infiltrating B cells, with potential engagement of infection. Meanwhile, the non-Hunner lesion subtype is a noninflammatory disorder with little evidence of bladder etiology. It is potentially associated with urothelial malfunction and neurophysiological dysfunction, and frequently presents with somatic and/or psychological symptoms, that commonly result in central nervous sensitization. Animal models of autoimmune cystitis and neurogenic sensitization might serve as disease models for the Hunner lesion and non-Hunner lesion subtypes, respectively. Here, we revisit the taxonomy of interstitial cystitis/bladder pain syndrome according to current research, and discuss its potential pathophysiology and representative animal models. Categorization of interstitial cystitis/bladder pain syndrome based on cystoscopy is mandatory to design optimized treatment and research strategies for each subtype. A tailored approach that specifically targets the characteristic inflammation and epithelial denudation for the Hunner lesion subtype, or the urothelial malfunction, sensitized/altered nervous system and psychosocial problems for the non-Hunner lesion subtype, is essential for better clinical management and research progress in this complex condition.

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“…Several preclinical studies have identified molecular changes induced by Li-ESWT in the bladder. In a uroplakin-induced bladder pain model, Li-ESWT significantly decreased the expression and secretion of local and systemic inflammatory markers, including TNF-α and nerve growth factor (NGF), which were increased after uroplakin 3A immunization [7]. In a rat model of cryoinjury-induced DU, Li-ESWT improved the expression of TGF-β1 and vascular endothelial growth factor (VEGF) as well as of Ki-67 [4].…”

Section: A C C E P T E D a R T I C L Ementioning

confidence: 99%

“…Increasing preclinical evidence supports the role of low intensity extracorporeal shockwave therapy (Li-ESWT) in the treatment of non-infectious cystitis and detrusor underactivity. In a variety of animal models including cyclophosphamide-induced cystitis, radiation cystitis, uroplakin-induced autoimmune interstitial cystitis, cryoinjury-induced detrusor underactivity, and diabetic underactive bladder, treatment with Li-ESWT was found to improve bladder dysfunction and pain, reduce the inflammatory response, ameliorate muscle contractility and bladder morphology [3][4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

The Effect of Low-Intensity Extracorporeal Shockwave Treatment on the Urinary Bladder in an Experimental Diabetic Rat Model

et al. 2021

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Increasing preclinical data support an impact of low intensity extracorporeal shockwave therapy (Li-ESWT) on the bladder. We investigated the molecular effect of Li-ESWT on the bladder of a streptozotocin induced diabetic rat model. Methods: Fifteen 8-week old male Wistar rats were randomized into 3 groups: a control group (Control bladder CB; n=5), a group of diabetic rats without treatment (diabetes mellitus DM, n=5) and a group of diabetic rats treated with Li-ESWT (DM-ESWT; n=5). For the induction of diabetes, a single intraperitoneal dose of streptozotocin (60mg/kg) was used. Twenty days after the induction of diabetes, each rat in group DM-ESWT received 300 shockwaves with an energy flux density of 0.09 mJ/mm 2. Sessions were repeated three times/week for two weeks, followed by a two-week washout period. Total RNA from bladder tissue was extracted, cDNA was synthesized and Quantitative Real Time Polymerase Chain Reaction was performed to analyze the expression pattern of the Transient Receptor Potential Vanilloid 1 (TRPV1), interleukin 1β (IL1b) and the muscarinic receptors M1, M2, and M3 (Chrm1, Chrm2, and Chrm3). Results: The expression of TRPV1, IL1b, and Chrm2 genes was significantly different between the three groups (p=0.002, <0.0001 and 0.011, respectively) (one-way ANOVA). In the DM group, the expression of all genes was increased in comparison with the control group, but statistical significance was observed only for TRPV1 and IL1b genes (p=0.002 and <0.0001, respectively). Li-ESWT significantly reduced the expression of IL1b and Chrm2 (p=0.001 and 0.011, respectively), whereas a tendency for reduced expression was noted for TRPV1 (p=0.069). Conclusions: The induction of diabetes mellitus was associated with increased expression of genes related to mechanosensation, inflammation/ischemia, and contraction in the rat bladder. Li-ESWT reduced the expression of IL1b, Chrm2 and lesser of TRPV1 receptor genes A c c e p t e d A r t i c l e-2-towards controls' levels, suggesting a therapeutic potential of this treatment modality for diabetic cystopathy.

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Treatment with low-energy shock wave alleviates pain in an animal model of uroplakin 3A-induced autoimmune interstitial cystitis/painful bladder syndrome

Cited by 14 publications

References 28 publications

A 3′UTR modification of the TNF-α mouse gene increases peripheral TNF-α and modulates the Alzheimer-like phenotype in 5XFAD mice

A 3′UTR modification of the TNF-α mouse gene increases peripheral TNF-α and modulates the Alzheimer-like phenotype in 5XFAD mice

Interstitial cystitis/bladder pain syndrome: The evolving landscape, animal models and future perspectives

The Effect of Low-Intensity Extracorporeal Shockwave Treatment on the Urinary Bladder in an Experimental Diabetic Rat Model

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