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Specific inhibition of ICAM-1 effectively reduces bladder inflammation in a rat model of severe non-bacterial cystitis.

Specific inhibition of ICAM-1 effectively reduces bladder inflammation in a rat model of severe non-bacterial cystitis.
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Zhang X, He H, Lu G, Xu T, Qin L, Wang X, Jin X, Liu B, Zhao Z, Shen Z, Shao Y,


Zhang X, He H, Lu G, Xu T, Qin L, Wang X, Jin X, Liu B, Zhao Z, Shen Z, Shao Y, (click to view)

Zhang X, He H, Lu G, Xu T, Qin L, Wang X, Jin X, Liu B, Zhao Z, Shen Z, Shao Y,

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Scientific reports 2016 Oct 266() 35672 doi 10.1038/srep35672
Abstract

The development and progression of bladder pain syndrome/interstitial cystitis (BPS/IC) is closely related to bladder inflammation. Intercellular adhesion molecule 1 (ICAM-1) is associated with bladder inflammation in BPS/IC. We investigated the effect of specific inhibition of ICAM-1 using an anti-ICAM-1 antibody (AIA) on bladder inflammation in a rat model of severe non-bacterial cystitis (NBC) resembling BPS/IC by evaluating the bladder inflammation grade, mast cell infiltration and related cytokines and receptors. We also compared the effects of AIA with the COX-2 inhibitor celecoxib and the neurokinin-1 receptor (NK1R) inhibitor aprepitant. Our NBC model was established by intraperitoneal injection of cyclophosphamide combined with intravesical protamine/lipopolysaccharide, which resulted in severe bladder inflammation and increased mast cell infiltration, similar to the pathological changes of BPS/IC. Inhibition of ICAM-1 by AIA significantly decreased the bladder inflammation grade and mast cell counts, which was accompanied by a reduction of purinergic receptors (P2X2/P2X3), prostaglandin E2, EP1/EP2 receptors, TNF-α, NK1R, and ICAM-1. Moreover, AIA showed superior effects to those of celecoxib and aprepitant treatment in improving the bladder inflammatory response. Our results suggest that ICAM-1 may play a critical role in bladder inflammation in severe NBC and may be used as a novel therapeutic target in non-bacterial bladder inflammation such as BPS/IC.

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