title: Cigarette smoke-induced urothelial cell damage: potential role of platelet-activating factor.
abstract: Cigarette smoking is an environmental risk factor associated with a variety of pathologies including cardiovascular disease, inflammation, and cancer development. 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. Previously, we determined that cigarette smoking was associated with bladder wall accumulation of platelet activating factor (PAF), a potent inflammatory mediator that facilitates transendothelial cell migration of inflammatory cells from the circulation. PAF has been shown to reduce expression of tight junctional proteins which could ultimately lead to increased urothelial cell permeability. In this study, we observed that cigarette smoke extract (CSE) treatment of human urothelial cells increases PAF production and PAF receptor expression and reduces wound healing ability. After exposure to cigarette smoke for 6 months, wild-type C57BL/6 mice displayed urothelial thinning and destruction which was not detected in iPLA2β-/-(enzyme responsible for PAF production) animals. We also detected increased urinary PAF concentration in IC/BPS patients when compared to controls, with an even greater increase in urinary PAF concentration in smokers with IC/BPS These data indicate that cigarette smoking is associated with urothelial cell damage that may be a result of increased PAF-PAF receptor interaction. Inhibition of iPLA2βactivity or blocking of the PAF-PAF receptor interaction could serve as a potential therapeutic target for managing cigarette smoke-induced bladder damage.
authors.affiliation: Department of Pathology, Saint Louis University School of Medicine, Saint Louis, Missouri.
authors.forename: Shannon E
authors.initials: SE
authors.lastname: Kispert
authors.affiliation: Department of Pathology, Saint Louis University School of Medicine, Saint Louis, Missouri.
authors.forename: John
authors.initials: J
authors.lastname: Marentette
authors.affiliation: Department of Obstetrics, Gynecology & Women's Health, Saint Louis University School of Medicine, Saint Louis, Missouri.
authors.forename: E Cristian
authors.initials: EC
authors.lastname: Campian
authors.affiliation: Department of Pathology, Saint Louis University School of Medicine, Saint Louis, Missouri.
authors.forename: T Scott
authors.initials: TS
authors.lastname: Isbell
authors.affiliation: Department of Pathology, Saint Louis University School of Medicine, Saint Louis, Missouri.
authors.forename: Hannah
authors.initials: H
authors.lastname: Kuenzel
authors.affiliation: Department of Pathology, Saint Louis University School of Medicine, Saint Louis, Missouri mchowaj@slu.edu.
authors.forename: Jane
authors.initials: J
authors.lastname: McHowat
mesh_terms: D000818:Animals; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010972:Platelet Activating Factor / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012906:Smoke; D012907:Smoking; D019459:Urothelium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
chemical_list: D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; D012906:Smoke; C039351:platelet activating factor receptor
keywords: Inflammation; interstitial cystitis; smoking; urothelium