Downregulation of toll-like receptor 4 and IL-6 following irradiation of the rat urinary bladder.
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 20 Gy or only sedated (controls) and killed 16 h to 14 days later. Rats were placed in a metabolic cage at 16 h, 3 days, 7 days and 14 days following bladder irradiation. The urinary bladders were harvested and analysed with qPCR, immunohistochemistry and/or Western blot for the expression of interferon (IFN)-γ, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, nitric oxide synthases (eNOS, iNOS and nNOS), tumour necrosis factor (TNF)-α 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 14 days 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.
Department of Pharmacology, University of Gothenburg, Gothenburg, Sweden.|Department of Oncology, University of Gothenburg, Gothenburg, Sweden.
D
D
Giglio
Department of Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden.
C
C
Wasén
Department of Pathology, University of Gothenburg, Gothenburg, Sweden.
J
J
Mölne
Department of Pharmacology, University of Gothenburg, Gothenburg, Sweden.
D
D
Suchy
Department of Radiation Physics, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
J
J
Swanpalmer
Department of Pharmacology, University of Gothenburg, Gothenburg, Sweden.
J
J
Jabonero Valbuena
Department of Pharmacology, University of Gothenburg, Gothenburg, Sweden.
G
G
Tobin
Department of Oncology, University of Gothenburg, Gothenburg, Sweden.
L
L
Ny
D000818:Animals; D015536:Down-Regulation / Q000502:physiology* / Q000528:radiation effects*; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D001743:Urinary Bladder / Q000378:metabolism* / Q000528:radiation effects*
D015850:Interleukin-6; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase
immune system; interleukin; irradiation; nitric oxide; toll like receptors; urinary bladder