title: Specific inhibition of ICAM-1 effectively reduces bladder inflammation in a rat model of severe non-bacterial cystitis.
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.
authors: Department of Urology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Xiang
authors: X
authors: Zhang
authors: Department of Urology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Hongchao
authors: H
authors: He
authors: Department of Urology, Ruijin Hospital North, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Guoliang
authors: G
authors: Lu
authors: Department of Urology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Tianyuan
authors: T
authors: Xu
authors: Department of Urology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Liang
authors: L
authors: Qin
authors: Department of Urology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Xianjin
authors: X
authors: Wang
authors: Department of Urology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Xingwei
authors: X
authors: Jin
authors: Department of Urology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Boke
authors: B
authors: Liu
authors: Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors: Zhonghua
authors: Z
authors: Zhao
authors: Department of Urology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.
authors: Zhoujun
authors: Z
authors: Shen
authors: Department of Urology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Department of Urology, Ruijin Hospital North, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Yuan
authors: Y
authors: Shao
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D000077608:Aprepitant; D000068579:Celecoxib / Q000494:pharmacology; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D003520:Cyclophosphamide; D018856:Cystitis, Interstitial / Q000139:chemically induced / Q000473:pathology* / Q000628:therapy*; D016207:Cytokines / Q000276:immunology; D005260:Female; D007167:Immunotherapy / Q000379:methods*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides; D008407:Mast Cells / Q000276:immunology; D009025:Morpholines / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists / Q000494:pharmacology; D011479:Protamines; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000473:pathology*
chemical_list: D000906:Antibodies; D052246:Cyclooxygenase 2 Inhibitors; D016207:Cytokines; C000609942:ICAM1 protein, rat; D008070:Lipopolysaccharides; D009025:Morpholines; D064729:Neurokinin-1 Receptor Antagonists; D011479:Protamines; D018799:Intercellular Adhesion Molecule-1; D000077608:Aprepitant; D003520:Cyclophosphamide; D000068579:Celecoxib