title: Labisia pumila var. alata reduces bacterial load by inducing uroepithelial cell apoptosis.
abstract: BACKGROUND
  Labisia pumila var. alata (LPva) is a traditional medicinal herb used by Malaysian women to treat many ailments of the genitourinary tract. Its phytoestrogenic properties suggest potential to prevent recurrent urinary tract infection (UTI) in women post menopause. The aim of this study was therefore to investigate the mechanisms of action of LPva in an in vitro model of UTI.
  
  
  METHODS
  Bladder epithelial cell lines T24 and 5637 and uropathogenic Escherichia coli (UPEC) strain CFT073 were used to model uroepithelial infection. The ability of LPva to induce programmed cell death was tested using the Annexin-V-FLUOS and TUNEL assays. Expression of caveolin-1, β1 integrin and antimicrobial peptides HBD-2 and LL-37 in response to LPva treatment and/or infection, was assessed using RT real-time PCR. Effects on protein expression were confirmed by Western blot analysis. Sensitivity and yeast agglutination assays were employed to determine if LPva had antimicrobial activities and/or interacted with type 1 fimbriae, respectively. Finally, bacterial adherence and invasion to cells treated with LPva was examined.
  
  
  RESULTS
  LPva induced uroepithelial apoptosis which was coupled with upregulated expression of caveolin-1 and downregulation of β1 integrin. LPva did not exhibit direct antimicrobial properties and did not influence antimicrobial peptide levels in cells. Additionally, LPva did not interact with type 1 fimbriae and did not affect adherence in comparison to non-treated control cells. However, LPva significantly reduced the number of intracellular UPEC in bladder epithelial cells.
  
  
  CONCLUSIONS
  Our findings suggest that LPva has beneficial applications against UPEC infection due to its ability to induce programmed cell death and reduce bacterial invasion of the uroepithelium.
authors.affiliation: Department of Microbiology, Tumour and Cell Biology, Division of Clinical Microbiology, Karolinska Institutet and Karolinska University Hospital, S-171 76 Stockholm, Sweden.
authors.forename: Mansor
authors.initials: M
authors.lastname: Fazliana
authors.forename: Nubia L
authors.initials: NL
authors.lastname: Ramos
authors.forename: Petra
authors.initials: P
authors.lastname: Lüthje
authors.forename: Musa
authors.initials: M
authors.lastname: Sekikubo
authors.forename: Asa
authors.initials: A
authors.lastname: Holm
authors.forename: W M
authors.initials: WM
authors.lastname: Wan Nazaimoon
authors.forename: Annelie
authors.initials: A
authors.lastname: Brauner
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D058491:Bacterial Load / Q000187:drug effects; D051242:Caveolin 1 / Q000378:metabolism; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects / Q000382:microbiology; D004926:Escherichia coli / Q000187:drug effects; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D029623:Primulaceae; D015854:Up-Regulation; D001743:Urinary Bladder / Q000187:drug effects* / Q000382:microbiology; D014552:Urinary Tract Infections / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D019459:Urothelium / Q000166:cytology / Q000187:drug effects* / Q000382:microbiology
chemical_list: D051242:Caveolin 1; D019012:Integrin beta1; D010936:Plant Extracts