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 iPLA2β activity or blocking of the PAF-PAF receptor interaction could serve as a potential therapeutic target for managing cigarette smoke-induced bladder damage.
Physiological reports. 2017 Mar [Epub]
Shannon E Kispert, John Marentette, E Cristian Campian, T Scott Isbell, Hannah Kuenzel, Jane McHowat
Department of Pathology, Saint Louis University School of Medicine, Saint Louis, Missouri., Department of Obstetrics, Gynecology & Women's Health, Saint Louis University School of Medicine, Saint Louis, Missouri., Department of Pathology, Saint Louis University School of Medicine, Saint Louis, Missouri .