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Smoking‐induced urothelial cell accumulation of platelet‐activating factor: Implications for interstitial cystitis/bladder pain syndrome
Author(s) -
McHowat Jane,
Marentette John,
Isbell T. Scott,
Campian E. Cristian
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.968.9
Subject(s) - interstitial cystitis , urothelial cell , platelet activating factor , medicine , urothelium , creatinine , urology , endocrinology , urinary bladder , urinary system
Interstitial cystitis/bladder pain syndrome (IC/BPS) may encompass many diseases with causes such as stress, irritants, previous bladder infections, a dysregulated immune response, inappropriate diet or cigarette smoking. We have determined previously that cigarette smoke extract (CSE) results in accumulation of platelet‐activating factor (PAF) via activation of calcium‐independent phospholipase A 2 and inhibition of PAF acetylhydrolase (PAF‐AH). We hypothesized that cigarette smoking may predispose smokers to IC/PBS via PAF accumulation in the bladder wall. Incubation of human urothelial cells (HUC) with cigarette smoke extract (CSE) resulted in a significant inhibition of PAF‐AH activity and PAF accumulation. Inhibition of HUC with CSE resulted in a decrease in electrical resistance and rate of wound healing. Histological examination of bladders removed from mice exposed to cigarette smoke showed urothelial cell thinning and sloughing. Immunohistological staining indicated an increase in PAF accumulation in the bladder wall of mice exposed to cigarette smoke when compared to room air. PAF content in the urine obtained from IC/BPS patients was greater than that observed in controls (PAF:creatinine ratio 13.5 ± 1.5 compared with 5.4 ± 0.6, n=3, p<0.05). PAF content was greater in IC/BPS patients who were current smokers (PAF: creatinine ratio 34.3 ± 10.4, n=3) than in IC/BPS patients who did not smoke. We conclude that cigarette smoking is associated with PAF accumulation in the bladder wall that could contribute to impairment of urothelial function in IC/BPS patients. Support or Funding Information Saint Louis University President's Research Fund