Abstract

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory bladder disease with multiple etiological contributors and risk factors associated with its development, including cigarette smoking. In a recently published manuscript, we have shown that smoking is associated with bladder wall inflammation and accumulation of platelet activating factor (PAF), a potent inflammatory mediator that facilitates transendothelial inflammatory cell migration and reduction in tight junction protein expression, which could contribute to urothelial cell dysfunction. PAF accumulation in response to cigarette smoking is primarily the result of the inhibition of PAF acetylhydrolase (PAF‐AH, the enzyme responsible for PAF hydrolysis and inactivation). The present study was designed to determine whether urine content of PAF or PAF‐AH activity can be used as an indicator of IC/BPS. For stability studies, voided urine specimens were collected from patients with and without a diagnosis of IC/BPS. Samples were stored at room temperature and frozen in liquid nitrogen at intervals up to 60 mins following voiding. PAF content and PAF‐AH activity were measured and normalized to creatinine. Measurement of PAF and PAF‐AH was consistent at all time intervals up to 60 mins, demonstrating stability following voiding. Addition of PAF internal standard to urine samples prior to analysis indicated a recovery of >96% PAF. PAF content in the urine of IC/BPS patients (1.16 ± 0.16 PAF:creatinine ratio, n=6, p<0.05) was significantly greater than that for non‐IC/BPS patients (0.37 ± 0.18 PAF:creatinine ratio, n=5). PAF content was also greater in IC/BPS patients who smoke (1.19 + 0.36 PAF:creatinine ratio, n=4, p<0.05) when compared to non‐IC/BPS patients. PAF‐AH activity was decreased in the urine of IC/BPS patients who were smokers (48.3 ± 2.4 PAF‐AH: creatinine ratio, n=4, p<0.05) or non‐smokers (40.0 ± 7.0 PAF‐AH: creatinine ratio, n=6, p<0.05) when compared to non‐smokers with no IC/BPS (64.6 ± 2.2 PAF‐AH:creatinine ratio, n=5). Our data demonstrate that urine content of PAF and/or PAF‐AH is stable at up to 60 mins storage at room temperature following voiding. Urinary PAF is increased in IC/BPS patients, and is likely the result of PAF‐AH inhibition. Future studies are required to determine the effect of cigarette smoking on the incidence and severity of IC/BPS.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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