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Downregulation of toll-like receptor 4 and IL-6 following irradiation of the rat urinary bladder

Journal article
Authors Daniel Giglio
Caroline Wasén
Johan Mölne
Dariusz Suchy
John Swanpalmer
J. Jabonero Valbuena
Gunnar Tobin
Lars Ny
Published in Clinical and Experimental Pharmacology and Physiology
Volume 43
Issue 7
Pages 698-705
ISSN 1440-1681
Publication year 2016
Published at Institute of Clinical Sciences, Department of Radiation Physics
Institute of Clinical Sciences, Department of Oncology
Institute of Biomedicine, Department of Pathology
Institute of Medicine, Department of Rheumatology and Inflammation Research
Institute of Neuroscience and Physiology, Department of Pharmacology
Pages 698-705
Language en
Links dx.doi.org/10.1111/1440-1681.12583
Keywords irradiation, urinary bladder, immune system, interleukin, toll like receptors, nitric oxide, nitric-oxide synthase, cyclophosphamide-induced cystitis, radiation, cystitis, escherichia-coli, expression, inflammation, inhibition, responses, mucosa, cells, Pharmacology & Pharmacy, Physiology
Subject categories Clinical Medicine

Abstract

The pathophysiology behind radiation cystitis is poorly understood. Here we investigated whether bladder irradiation affects the immune system of the rat urinary bladder. Female rats were sedated and exposed to one single radiation dose of 20Gy or only sedated (controls) and killed 16h to 14days later. Rats were placed in a metabolic cage at 16h, 3days, 7days and 14days following bladder irradiation. The urinary bladders were harvested and analysed with qPCR, immunohistochemistry and/or Western blot for the expression of interferon (IFN)-, interleukin (IL)-1, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, nitric oxide synthases (eNOS, iNOS and nNOS), tumour necrosis factor (TNF)- and toll-like receptor 4 (TLR4). Urine was collected and analysed for IL-6 and nitrite (reflecting nitric oxide activity) with ELISA and the Griess reaction, respectively. Irradiation increased bladder frequency and decreased voiding volumes 14days following bladder irradiation. Bladder irradiation increased the expression of IL-10 and collagen in the bladder, while TLR4 and IL-6 expressions were decreased in the urothelium concomitantly with a decrease in mast cells in the submucosa and urine levels of IL-6 and nitrite. The present findings show that bladder irradiation leads to urodynamic changes in the bladder and may suppress important immunoregulatory pathways in the urinary bladder.

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