title: Epigallocatechin gallate attenuates interstitial cystitis in human bladder urothelium cells by modulating purinergic receptors.
abstract: BACKGROUND
  Epigallocatechin gallate (EGCG) has exhibited antitumor properties against bladder cancer. However, its effects in interstitial cystitis (IC) have not been investigated.
  
  
  METHODS
  Here, we performed repeated cystoscopy and re-biopsy of bladder mucosa before and after intravesical irrigation of EGCG in eight patients diagnosed with IC based on clinical and histopathologic assessments. Six normal bladder tissue samples were obtained from age-, race-, and sex-matched asymptomatic control subjects. IC symptom index was used to compare the therapeutic effect in IC patients. Patient-derived bladder epithelial cells were cultured and cell stretch experiments and ATP assays were performed. The expression of purinergic receptors X1, X2, and X3, and Y1, Y2, and Y11, in biopsied samples was detected by Western blotting and real-time polymerase chain reaction, respectively. Moreover, the expression of inducible NO synthase, phosphorylated Akt, and phosphorylated NF-κB was also assessed.
  
  
  RESULTS
  All EGCG-treated patients demonstrated different extents of remission of symptoms. We found a significant upregulation in P2X1, P2X2, and P2X3 receptor proteins and P2Y1, P2Y2, and P2Y11 receptor transcripts in IC patients. However, EGCG therapy attenuated the expression of all purinergic receptors. In addition, EGCG demonstrated prominent antioxidative and antiinflammatory effects via inhibition of the upregulation of iNOS and phosphorylated NF-κB. Furthermore, the stretch-activated release of ATP in cultured bladder urothelial cells was greater in cells derived from IC patients, compared with those from the control patients, but EGCG, at all concentrations tested, effectively abolished the increase in ATP release from stretched IC patient-derived cells.
  
  
  CONCLUSIONS
  Our study suggests that inhibition of the expression of purinergic receptors and ATP release in urothelial cells by EGCG supports further development of EGCG as a novel therapeutic option for IC.
authors.affiliation: Department of Urology & Surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai, PR China. liumin@tongji.edu.cn
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Xu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Feng
authors.forename: Feng-Qiang
authors.initials: FQ
authors.lastname: Yang
authors.forename: Jun
authors.initials: J
authors.lastname: Luo
authors.forename: Wei
authors.initials: W
authors.lastname: Zhai
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Che
authors.forename: Guang-Chun
authors.initials: GC
authors.lastname: Wang
authors.forename: Jun-Hua
authors.initials: JH
authors.lastname: Zheng
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D016022:Case-Control Studies; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002478:Cells, Cultured; D018856:Cystitis, Interstitial / Q000188:drug therapy* / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011983:Receptors, Purinergic / Q000378:metabolism*; D019459:Urothelium / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000975:Antioxidants; D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate; D002392:Catechin; C045651:epigallocatechin gallate; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II