Deletion or pharmacological blockade of TLR4 confers protection against cyclophosphamide-induced mouse cystitis
| العنوان: | Deletion or pharmacological blockade of TLR4 confers protection against cyclophosphamide-induced mouse cystitis |
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| المؤلفون: | Fabiano B. Calmasini, Eduardo C. Alexandre, Soraia K.P. Costa, Antonio G. Soares, Edson Antunes, Mariana G. de Oliveira, Fabíola Z. Mónica, Edith B G Tavares |
| المصدر: | American Journal of Physiology-Renal Physiology. 315:F460-F468 |
| بيانات النشر: | American Physiological Society, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, medicine.medical_specialty, Carbachol, Cyclophosphamide, Physiology, Urinary system, Urinary Bladder, Anti-Inflammatory Agents, Cystitis, Interstitial, 030232 urology & nephrology, Urination, urologic and male genital diseases, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Animals, Medicine, Receptor, Peroxidase, Mice, Knockout, Receptor, Muscarinic M3, Receptor, Muscarinic M2, Sulfonamides, Urinary bladder, medicine.diagnostic_test, Interleukin-6, Tumor Necrosis Factor-alpha, business.industry, Interstitial cystitis, Cystometry, medicine.disease, Blockade, Mice, Inbred C57BL, Toll-Like Receptor 4, Adaptor Proteins, Vesicular Transport, Disease Models, Animal, Urodynamics, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Myeloid Differentiation Factor 88, Inflammation Mediators, business, Signal Transduction, medicine.drug |
| الوصف: | Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a chronic inflammatory disease without consistently effective treatment. We investigate the role of toll-like receptor 4 (TLR4) on voiding dysfunction and inflammation in the cyclophosphamide (CYP)-induced mouse cystitis. Male C57BL/6 [wild-type, (WT)] and/or TLR4 knockout (TLR4−/−) mice were treated with an injection of CYP (300 mg/kg, 24 h) or saline (10 ml/kg). The pharmacological blockade of the TLR4 by resatorvid (10 mg/kg) was also performed 1 h prior CYP-injection in WT mice. Urodynamic profiles were assessed by voiding stain on filter paper and filling cystometry. Contractile responses to carbachol were measured in isolated bladders. In CYP-exposed WT mice, mRNA for TLR4, myeloid differentiation primary response 88, and TIR-domain-containing adapter-inducing interferon-β increased by 45%, 72%, and 38%, respectively ( P < 0.05). In free-moving mice, CYP-exposed mice exhibited a higher number of urinary spots and smaller urinary volumes. Increases of micturition frequency and nonvoiding contractions, concomitant with decreases of intercontraction intervals and capacity, were observed in the filling cystometry of WT mice ( P < 0.05). Carbachol-induced bladder contractions were significantly reduced in the CYP group, which was paralleled by reduced mRNA for M2 and M3 muscarinic receptors. These functional and molecular alterations induced by CYP were prevented in TLR4−/− and resatorvid-treated mice. Additionally, the increased levels of inflammatory markers induced by CYP exposure, myeloperoxidase activity, interleukin-6, and tumor necrosis factor-alpha were significantly reduced by resatorvid treatment. Our findings reveal a central role for the TLR4 signaling pathway in initiating CYP-induced bladder dysfunction and inflammation and thus emphasize that TLR4 receptor blockade may have clinical value for IC/BPS treatment. |
| تدمد: | 1522-1466 1931-857X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::847ccf24b060f30b073788e2c7b577c2Test https://doi.org/10.1152/ajprenal.00100.2018Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....847ccf24b060f30b073788e2c7b577c2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221466 1931857X |
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