title: Quantification and comparison of toll-like receptor expression and responsiveness in primary and immortalized human female lower genital tract epithelia.
abstract: OBJECTIVE
  To better understand innate immune responses to sexually-transmitted infection (STI) and the appropriateness of epithelial cell (EC) models of the vaginal and cervical mucosa, quantified toll-like receptor (TLR) expression from a population of women is needed.
  
  
  METHODS
  TLR gene expression was quantified in primary and immortalized endocervical, ectocervical, and vaginal EC from multiple donors. TLR bioactivity was evaluated by cytokine elaboration.
  
  
  RESULTS
  TLR1-3 and 5-9 were expressed in each EC type with TLR2, 3, 5, 6 and CD14 expressed most abundantly. TLR4 was expressed by endocervical and vaginal EC. Agonist stimulation of TLR2, 3, 5 and 6 elicited cytokines. TLR4 and 7-9 were minimally expressed and were not consistently bioactive. Immortalized EC generally modeled primary cultures but elaborated significantly reduced cytokine levels.
  
  
  CONCLUSIONS
  TLR expression patterns were remarkably conserved across the study population and evaluated tissues indicating a predictable responsiveness to STI. The results support cautious use of immortalized cells for genital tract modeling.
authors.affiliation: Department of Pediatrics, Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX 77555-0436, USA.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Herbst-Kralovetz
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Quayle
authors.forename: Mercedes
authors.initials: M
authors.lastname: Ficarra
authors.forename: Sheila
authors.initials: S
authors.lastname: Greene
authors.forename: William A
authors.initials: WA
authors.lastname: Rose
authors.forename: Ralph
authors.initials: R
authors.lastname: Chesson
authors.forename: Rae Ann
authors.initials: RA
authors.lastname: Spagnuolo
authors.forename: Richard B
authors.initials: RB
authors.lastname: Pyles
mesh_terms: D000328:Adult; D002584:Cervix Uteri / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000276:immunology / Q000378:metabolism; D003521:Cyclopropanes; D004075:Diglycerides / Q000276:immunology; D004848:Epithelium / Q000276:immunology / Q000378:metabolism; D005260:Female; D005408:Flagellin; D020869:Gene Expression Profiling; D006151:Guanosine / Q000031:analogs & derivatives; D006801:Humans; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides; D009842:Oligopeptides / Q000276:immunology; D012330:RNA, Double-Stranded; D012749:Sexually Transmitted Diseases / Q000276:immunology; D051193:Toll-Like Receptors / Q000096:biosynthesis* / Q000276:immunology; D014621:Vagina / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
chemical_list: D018932:Chemokine CCL2; D003521:Cyclopropanes; D004075:Diglycerides; C460864:FSL-1 lipoprotein, synthetic; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; C508012:N2-cyclopropylamine-guanosine; D009842:Oligopeptides; D012330:RNA, Double-Stranded; D051193:Toll-Like Receptors; D006151:Guanosine; D005408:Flagellin