Inflammatory process in interstitial cystitis and evaluation of the influence of cannabinoid receptor agonists in urinary bladder - from cells to patients

Interstitial cystitis (IC) is a urinary bladder disorder with no obvious histopathology or bacterial infection. Its prevalence is up to 2% in females, diagnosed annually, and its incidence is increasing globally. Since the etiology of IC is poorly understood, this illness still lacks an efficient cure, as the current treatment is still not successful in more than a third of the patient population. A general indicator of IC is an increase in inflammatory markers which is supposed to induce altered urothelial barrier function and abnormal urothelial sensory / signaling function that further induce inflammation, causing a vicious circle. However, the mechanism by which inflammation interacts with both defects is poorly understood. Studies of barrier components and receptors involved in urothelial signaling in healthy and diseased bladders lack a multidisciplinary approach, which would include epigenetic, proteomic and cell-biological approaches. This shortcoming leads to often contradictory and confusing conclusions. Such multilevel studies have not been done yet, mainly because of the technically demanding cryo-electron microscopic and proteomic methods required for that. Additionally, epigenetic studies that could explain why chronic symptoms, similar to those of bacterial cystitis, persist for years in women with IC without an obvious cause have not been used sufficiently in urothelial tissue. Since the exploration of non-psychogenic cannabinoids as anti-inflammatory treatment is exponentially growing recently, the aim of the present study is to determine whether selected cannabinoids can reduce inflammation of urinary bladder associated with interstitial cystitis and whether they can recover the barrier function of this tissue. Our multidisciplinary epigenetic, proteomic and cell biological analysis of urothelial cells collected from IC patients, experimental animals and biomimetic cell culture system will provide evidence for the potential of the cannabinoid treatment in case of IC . The ultimate goal of this study is to better understand the molecular mechanisms of urothelial hypersensitivity in chronic urinary bladder inflammation in IC. The results of this study have a realistic chance to provide the basis for development of new drugs leading to a better treatment of IC.