title: Regulation of cyclooxygenase-2 expression in human bladder epithelial cells infected with type I fimbriated uropathogenic E. coli.
abstract: The type 1 fimbriae of uropathogenic Escherichia coli (UPEC) have been described as important for the establishment of bladder infections and urinary tract infections (UTI). Urinary prostaglandin (PG) levels and cyclooxygenase (COX)-2 expression in urine particulates may increase with infectious and inflammatory processes, including UTIs. We investigated the mechanisms underlying the modulation of COX-2 expression through the invasion of type 1 fimbriated UPEC strain J96 (J96-1) in human bladder 5637 cells. Bladder 5637 cells infected with J96-1 induced increases in the expression of COX-2 and secretion of PGE(2) . By using specific inhibitors and short hairpin RNA (shRNA), we have demonstrated that the activation of extracellular signal-related kinase (ERK), c-Jun-NH(2) -terminal kinase (JNK) and p38 MAPK pathways is critical for J96-1-induced COX-2 expression. Luciferase reporters and chromatin immunoprecipitation assays suggest that J96-1 invasion increases NF-κB- and AP-1-DNA-binding activities in 5637 cells. Inhibition of NF-κB and AP-1 activations blocked the J96-1-induced COX-2 promoter activity and expression. The effect of J96-1 on 5637 cell signalling and COX-2 expression is mediated by Toll-like receptor (TLR)-4. In summary, our findings provide the molecular pathways underlying type 1 fimbriated J96-dependent COX-2 expression in 5637 cells, providing insight into the function of UPEC invasion in bladder epithelial cells.
authors.affiliation: Division of Nephrology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Te-Chuan
authors.initials: TC
authors.lastname: Chen
authors.forename: Jen-Pi
authors.initials: JP
authors.lastname: Tsai
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Huang
authors.forename: Chih-Chuan
authors.initials: CC
authors.lastname: Teng
authors.forename: Shao-Ju
authors.initials: SJ
authors.lastname: Chien
authors.forename: Hsing-Chun
authors.initials: HC
authors.lastname: Kuo
authors.forename: Wen-Shih
authors.initials: WS
authors.lastname: Huang
authors.forename: Cheng-Nan
authors.initials: CN
authors.lastname: Chen
mesh_terms: D019677:Artificial Gene Fusion; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D015232:Dinoprostone / Q000378:metabolism; D004847:Epithelial Cells / Q000201:enzymology* / Q000382:microbiology*; D017930:Genes, Reporter; D054884:Host-Pathogen Interactions; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D056689:Uropathogenic Escherichia coli / Q000472:pathogenicity*
chemical_list: C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D008156:Luciferases; D051546:Cyclooxygenase 2; D015232:Dinoprostone