286: Link Between Cytokine Expression and Augmented Purinergic Signaling in Interstitial Cystitis (IC) Bladder Urothelial Cells (BUC)

2006 ◽  
Vol 175 (4S) ◽  
pp. 95-95 ◽  
Author(s):  
Todd J. Lehrfeld ◽  
Yan Sun ◽  
Toby C. Chai
Keyword(s):  
Interstitial Cystitis ◽  
Purinergic Signaling ◽  
Cytokine Expression ◽  
Urothelial Cells

Augmented extracellular ATP signaling in bladder urothelial cells from patients with interstitial cystitis

2006 ◽  
Vol 290 (1) ◽  
pp. C27-C34 ◽  
Author(s):  
Yan Sun ◽  
Toby C. Chai
Keyword(s):  
Interstitial Cystitis ◽  
Purinergic Signaling ◽  
Atp Release ◽  
Extracellular Atp ◽  
Luciferase Assay ◽  
Heparin Binding ◽  
Urothelial Cells ◽  
Atp Levels ◽  
And Control ◽  
Atp Signaling

Interstitial cystitis (IC) is an idiopathic hypersensory condition of the bladder associated with increased urinary ATP and increased stretch-activated ATP release by bladder urothelial cells (BUCs), suggesting augmented purinergic signaling in the bladder. To test this theory further, monolayers of cultured BUCs derived from bladder biopsies obtained from patients with IC and control patients were stimulated with 10–30 μM ATP with subsequent measurement of extracellular ATP levels using the luciferin-luciferase assay. Stimulation with 30 μM ATP resulted in IC supernatant containing several-fold more ATP than control BUCs initially, followed by a slower decrease in ATP levels. This difference in ATP levels was not completely due to activity of cellular ecto-ATPase, because blockade with ARL67156 did not normalize the difference. Exposure to hypotonic solutions resulted in similar extracellular ATP concentrations in IC and control BUCs, but there was a slower decrease in ATP levels in IC supernatants. Treatment of IC BUCs with 10–40 μM suramin, a nonspecific P2 receptor antagonist, significantly attenuated the IC BUC response to extracellular ATP, restoring IC BUCs to a control phenotype. Pretreatment of IC BUCs with 20 ng/ml of heparin-binding EGF-like growth factor (HB-EGF), which previously has been shown to be decreased in IC urine specimens, also restored IC BUCs to a control phenotype with respect to response to ATP stimulation. In conclusion, IC BUCs have augmented extracellular ATP signaling that could be blocked by suramin and HB-EGF. These findings suggest the possible development of future novel therapeutic techniques.

EGF and HB-EGF modulate inward potassium current in human bladder urothelial cells from normal and interstitial cystitis patients

2007 ◽  
Vol 292 (1) ◽  
pp. C106-C114 ◽  
Author(s):  
Yan Sun ◽  
Mingkui Chen ◽  
Benjamin H. Lowentritt ◽  
P. Sean Van Zijl ◽  
Kristopher R. Koch ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Interstitial Cystitis ◽  
Potassium Current ◽  
Purinergic Signaling ◽  
Potassium Conductance ◽  
Heparin Binding ◽  
Urothelial Cells ◽  
Epidermal Growth ◽  
Dose Dependent Decrease

Interstitial cystitis (IC) is an idiopathic condition characterized by bladder hyperalgesia. Studies have shown cytokine and purinergic signaling abnormalities in cultured bladder urothelial cells (BUC) from IC patients. We performed single-cell electrophysiological studies in both normal and IC BUC. A strongly inward rectifying potassium current with conductance of the Kir2.1 channel was identified in normal BUC. This current was significantly reduced in IC BUC. Kir2.1 protein and mRNA were detected in both IC and normal BUC. Epidermal growth factor (EGF) caused a dose-dependent decrease in the inward potassium current in normal BUC. EGF is secreted in higher amounts by IC BUC and is known to decrease Kir2.1 conductance by phosphorylation of Kir2.1. Genistein, a nonspecific phosphorylation inhibitor, increased the inward potassium current in IC BUC and blocked the effect of EGF on normal BUC. Treatment of IC BUC with heparin-binding epidermal growth factor-like growth factor (HB-EGF), previously shown to be secreted in lower amounts by IC BUC, significantly increased inward potassium current. These data show that the inward potassium current in BUC can be modulated by EGF and HB-EGF. Changes in BUC membrane potassium conductance caused by altered levels of EGF and HB-EGF may therefore play a role in the pathophysiology of IC.

Differentiation Associated Changes in Gene Expression Profiles of Interstitial Cystitis and Control Urothelial Cells

2008 ◽  
Vol 180 (6) ◽  
pp. 2681-2687 ◽  
Author(s):  
Deborah R. Erickson ◽  
Steven R. Schwarze ◽  
Justin K. Dixon ◽  
Curtis J. Clark ◽  
Matt A. Hersh
Keyword(s):  
Gene Expression ◽  
Interstitial Cystitis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Urothelial Cells ◽  
And Control

scholarly journals Loss of prostaglandin E2 release from immortalized urothelial cells obtained from interstitial cystitis patient bladders

2008 ◽  
Vol 294 (5) ◽  
pp. F1129-F1135 ◽  
Author(s):  
Prerna Rastogi ◽  
Alice Rickard ◽  
Nikolay Dorokhov ◽  
David J. Klumpp ◽  
Jane McHowat
Keyword(s):  
Arachidonic Acid ◽  
Interstitial Cystitis ◽  
Prostaglandin E ◽  
Arachidonic Acid Release ◽  
Urothelial Cells ◽  
Cell Numbers ◽  
Interstitial Cystitis Patient ◽  
Acid Release ◽  
Increased Susceptibility ◽  
Stimulation Of

Interstitial cystitis (IC) is associated with increased activated mast cell numbers in the bladder and impairment of the barrier function of the urothelium. We stimulated immortalized urothelial cells derived from the inflamed region of IC bladders (SR22A or SM28 abn) or from healthy bladders (PD07i or PD08i) with tryptase and measured phospholipase A2 (PLA2) activity and the resultant release of arachidonic acid and prostaglandin E2 (PGE2). Tryptase stimulation of either PD07i or SR22A resulted in similar increases in PLA2 activity and arachidonic acid release. However, tryptase stimulation of SR22A and SM28 abn did not result in a significant increase in PGE2 release compared with the increase in PGE2 release from tryptase-stimulated PD07i and PD08i cells. Expression of mRNA for cyclooxygenase-2 and PGE synthase was lower and mRNA for 15-hydroxyprostaglandin dehydrogenase was higher in SR22A compared with PD07i, suggesting that both decreased synthesis and increased metabolism are responsible for the lack of a PGE2 response in tryptase-stimulated SR22A cells. Since PGE2 is a cytoprotective eicosanoid, the failure to produce this metabolite in cells isolated from the IC bladder may represent an increased susceptibility to damage by proinfammatory stimuli.

Cytokine Expression in Patients with Bladder Pain Syndrome/Interstitial Cystitis ESSIC Type 3C

2014 ◽  
Vol 192 (5) ◽  
pp. 1564-1568 ◽  
Author(s):  
Yr Logadottir ◽  
Dick Delbro ◽  
Magnus Fall ◽  
Inger Gjertsson ◽  
Pernilla Jirholt ◽  
...  
Keyword(s):  
Interstitial Cystitis ◽  
Pain Syndrome ◽  
Bladder Pain Syndrome ◽  
Cytokine Expression ◽  
Bladder Pain
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