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.
Highlights
(group 1) had no edema or inflammation. (B) Cystitis model rats had obvious inflammation, including extensive submucosa edema and marked microhemorrhage accompanied by a significantly thinner urothelium. (C) Model +celecoxib rats had severe vascular proliferation, microhemorrhage, and errhysis with edema of the submucosa. (D) Model +aprepitant rats showed slight congestion of the microangium and severe congestion of the submucosa. (E) Model +AIA rats had no obvious changes except for slight edema
We investigated the involvement of intercellular adhesion molecule-1 (ICAM-1) in bladder inflammation in an non-bacterial cystitis (NBC) rat model, which shows similar inflammatory characteristics to IC
We found that the specific inhibition of ICAM-1 significantly attenuated bladder inflammation and mast cell infiltration, accompanied by a reduction of related inflammatory cytokines and receptors (P2X3 and P2Y2 receptors, prostaglandin E2 (PGE2), EP1/EP2 receptor, neurokinin-1 receptor (NK1R), TNF-α, and ICAM-1)
Summary
(group 1) had no edema or inflammation. (B) Cystitis model rats (group 2) had obvious inflammation, including extensive submucosa edema and marked microhemorrhage accompanied by a significantly thinner urothelium. (C) Model +celecoxib rats (group 3) had severe vascular proliferation, microhemorrhage, and errhysis with edema of the submucosa. (D) Model +aprepitant rats (group 4) showed slight congestion of the microangium and severe congestion of the submucosa. (E) Model +AIA rats (group 5) had no obvious changes except for slight edema. Mechanism by which hyaluronic acid can relieve the symptoms of BPS/IC12 All these publications strongly suggest that ICAM-1 might play a vital role in bladder inflammation of BPS/IC. We demonstrated that this NBC rat model was more suitable than other models that use intraperitoneal CYP or intravesical PS/LPS alone to mimic bladder lesions of BPS/IC patients[10]. Using this NBC model, we investigated the effect of blocking ICAM-1 with a specific anti-ICAM-1 antibody on bladder inflammation and compared its efficacy with celecoxib and aprepitant
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
