title: Dietary flavonoid luteolin attenuates uropathogenic Escherichia. Coli invasion of the urinary bladder.
abstract: Uropathogenic Escherichia coli (UPEC), the primary uropathogen, adhere to and invade bladder epithelial cells (BECs) to establish a successful urinary tract infection (UTI). Emerging antibiotic resistance requires novel nonantibiotic strategies. Our previous study indicated that luteolin attenuated adhesive and invasive abilities as well as cytotoxicity of UPEC on T24 BECs through down-regulating UPEC virulence factors. The aims of this study were to investigate the possible function of the flavonoid luteolin and the mechanisms by which luteolin functions in UPEC-induced bladder infection. Firstly, obvious reduction of UPEC invasion but not adhesion were observed in luteolin-pretreated 5637 and T24 BECs sa well as mice bladder via colony counting. The luteolin-mediated suppression of UPEC invasion was linked to elevated levels of intracellular cAMP induced by inhibiting the activity of cAMP-phosphodiesterases (cAMP-PDEs), which resulting activation of protein kinase A, thereby negatively regulating Rac1-GTPase-mediated actin polymerization. Furthermore, p38 MAPK was primarily and ERK1/2 was partially involved in luteolin-mediated suppression of UPEC invasion and actin polymerization, as confirmed with chemical activators of p38 MAPK and ERK1/2. These data suggest that luteolin can protect bladder epithelial cells against UPEC invasion. Therefore, luteolin or luteolin-rich products as dietary supplement may be beneficial to control the UPEC-related bladder infections, and cAMP-PDEs may be a therapy target for UTIs treatment. © 2016 BioFactors, 42(6):674-685, 2016.
authors.affiliation: Research Unit of Infection and Immunity, Department of Pathophysiology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu, China.
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Shen
authors.affiliation: Research Unit of Infection and Immunity, Department of Pathophysiology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Teng
authors.affiliation: Research Unit of Infection and Immunity, Department of Pathophysiology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu, China.
authors.forename: Kai-Hui
authors.initials: KH
authors.lastname: Sha
authors.affiliation: Research Unit of Infection and Immunity, Department of Pathophysiology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu, China.
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Research Unit of Infection and Immunity, Department of Pathophysiology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu, China.
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Yang
authors.affiliation: Research Unit of Infection and Immunity, Department of Pathophysiology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu, China.
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Guo
authors.affiliation: Research Unit of Infection and Immunity, Department of Pathophysiology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu, China.
authors.forename: Lai-Bin
authors.initials: LB
authors.lastname: Ren
authors.affiliation: Research Unit of Infection and Immunity, Department of Pathophysiology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu, China.
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Research Unit of Infection and Immunity, Department of Pathophysiology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu, China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Li
authors.affiliation: Research Unit of Infection and Immunity, Department of Pathophysiology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu, China.|Sichuan University 985 Project-Science and Technology Innovation Platform for Novel Drug Development, Sichuan University, Chengdu, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Huang
mesh_terms: D000199:Actins / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001422:Bacterial Adhesion / Q000187:drug effects; D019587:Dietary Supplements; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D047311:Luteolin / Q000008:administration & dosage*; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D009479:Neuropeptides / Q000378:metabolism; D055503:Protein Multimerization; D014552:Urinary Tract Infections / Q000382:microbiology / Q000517:prevention & control*; D056689:Uropathogenic Escherichia coli / Q000187:drug effects* / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; D000900:Anti-Bacterial Agents; D009479:Neuropeptides; C484602:Rac1 protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020830:rac1 GTP-Binding Protein; D047311:Luteolin
keywords: UPEC invasion; actin polymerization; cAMP phosphodiesterases; luteolin; urinary tract infections