Redistribution of calcium‐independent phospholipase A2 isoforms in IC/PBS urothelial cells (488.2)

Abstract

Interstitial cystitis/painful bladder syndrome (IC/PBS) is associated with impairment of urothelial barrier function, activated mast cells and neurogenic inflammation. We have demonstrated that urothelial cell calcium‐independent PLA2 (iPLA2) is activated by tryptase, resulting in platelet‐activating factor (PAF) production. We used immortalized urothelial cells isolated from normal and IC/PBS patients to determine whether there are differences in PAF production. We identified the two predominant mammalian iPLA2 isoforms, iPLA2β and iPLA2γ, in urothelial cells. IC/PBS cells demonstrated a decrease in iPLA2γ and an increase in iPLA2β immunoprotein when compared to normal cells. Selective inhibition of iPLA2 isoforms demonstrated that the majority of iPLA2 activity in normal urothelium represents iPLA2γ whereas that in IC/PBS urothelium is iPLA2β. Greater PAF production and PMN adherence was observed in tryptase‐stimulated IC/PBS when compared to normal urothelial cells. both normal and IC/PBS urothelial cells. Increased PAF production and PMN adherence was completely blocked when tryptase‐stimulated cells were pretreated with (S)‐BEL to inhibit iPLA2β. PMN adherence was blocked when PMN were pretreated with ginkgolide B to block the PAF receptor. A redistribution of iPLA2 isoforms in IC/PBS may represent a novel therapeutic target to manage IC/PBS.Grant Funding Source: Supported by DK 66119