title: Translocation of NF-κB and expression of cyclooxygenase-2 are enhanced by ketamine-induced ulcerative cystitis in rat bladder.
abstract: The number of ketamine abusers has increased significantly recently. Ketamine abusers exhibit urinary frequency, urgency, and at times urinary incontinence. Our aim was to investigate the role of transcription factor NF-κB and cyclooxygenase (COX)-2 in ketamine-induced cystitis. Sprague-Dawley rats were distributed into three groups, which received saline or treatment with ketamine or ketamine combined with a Cox-2 inhibitor (parecoxib). In addition, the toxic effect of ketamine and its metabolites were examined by primary urothelial cell culture. The ketamine-treated group displayed bladder hyperactivity and decreased bladder capacity. Treatment with ketamine + COX-2 inhibitor prevented these bladder dysfunctions. These bladder dysfunctions were accompanied by increases in the expression of NF-κB and COX-2 at the protein and mRNA levels. Ketamine treatment also enhanced bladder interstitial fibrosis, whereas ketamine + Cox-2 inhibitor decreased the intensity of fibrosis. Treatment of primary urothelial cells in vitro with ketamine or urine obtained from ketamine-treated rats stimulated the expression of NF-κB p65 and COX-2. Ketamine also initiated NF-κB translocation from cell cytoplasm to nucleus. Treatment with NF-κB inhibitor suppressed Cox-2 mRNA expression. Promoter-deletion analysis revealed that NF-κB was a necessary transcription factor for COX-2 gene (Ptgs2) activation. These results demonstrate that the regulation of COX-2 via the NF-κB pathway is involved in the inflammatory signaling of ketamine-induced cystitis in rat urinary bladder.
authors.affiliation: Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan; Department of Urology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Yung-Shun
authors.initials: YS
authors.lastname: Juan
authors.affiliation: Graduate Institute of Medical Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yi-Lun
authors.initials: YL
authors.lastname: Lee
authors.affiliation: Center of Excellence for Environmental Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Obstetrics and Gynecology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Cheng-Yu
authors.initials: CY
authors.lastname: Long
authors.affiliation: Department of Medical Genetics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Jhen-Hong
authors.initials: JH
authors.lastname: Wong
authors.affiliation: Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan.
authors.forename: Mei-Yu
authors.initials: MY
authors.lastname: Jang
authors.affiliation: Graduate Institute of Medical Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Jian-He
authors.initials: JH
authors.lastname: Lu
authors.affiliation: Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan; Department of Urology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Wen-Jeng
authors.initials: WJ
authors.lastname: Wu
authors.affiliation: Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Yen-Shun
authors.initials: YS
authors.lastname: Huang
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan; Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taipei, Taiwan; Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan; Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Electronic address: wcc@tmu.edu.tw.
authors.forename: Wei-Chiao
authors.initials: WC
authors.lastname: Chang
authors.affiliation: Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan. Electronic address: u9181002@gmail.com.
authors.forename: Shu-Mien
authors.initials: SM
authors.lastname: Chuang
mesh_terms: D000818:Animals; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D003556:Cystitis / Q000139:chemically induced / Q000378:metabolism*; D005260:Female; D006801:Humans; D007649:Ketamine; D016328:NF-kappa B / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D007649:Ketamine; D051546:Cyclooxygenase 2