Antiviral responses of human Fallopian tube epithelial cells to toll-like receptor 3 agonist poly(I:C)

Fertil Steril. 2008 May;89(5 Suppl):1497-506. doi: 10.1016/j.fertnstert.2007.05.023. Epub 2007 Jul 31.

Abstract

Objective: To examine the expression of toll-like receptors (TLR) by primary human Fallopian tube epithelial cells (FTEC) and to determine whether exposure to the TLR3 agonist poly(I:C) induces an antiviral response.

Design: Tissue culture study.

Setting: University medical center.

Patient(s): Premenopausal women undergoing hysterectomy.

Intervention(s): Primary human FTEC were grown to confluence and high transepithelial resistance and treated with TLR agonists. Conditioned media was collected and RNA was extracted and analyzed for the expression of cytokines, chemokines, and antimicrobial genes.

Main outcome measure(s): The RNA was analyzed by real-time polymerase chain reaction and protein levels were assessed by enzyme-linked immunosorbent assay.

Result(s): The FTEC were demonstrated to express TLR1-9 but not 10. Treatment of FTEC with TLR3 agonist poly(I:C) resulted in increased expression of interleukin-8, tumor-necrosis factor alpha, human beta-defensin 2, interferon beta, and interferon stimulated genes myxovirus resistance gene 1, 2',5'-oligoadenylate synthetase, and protein kinase R. Additionally, FTEC exposed to poly(I:C) also resulted in the induction of TLR2, TLR3, and TLR7.

Conclusion(s): Our results suggest that FTEC are sensitive to viral infection and/or exposure to viral double-stranded RNA and can respond by secreting proinflammatory cytokines that mediate the initiation of an inflammatory response as well as expressing genes that can directly inhibit viral replication.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 2',5'-Oligoadenylate Synthetase / genetics
  • 2',5'-Oligoadenylate Synthetase / metabolism
  • Cells, Cultured
  • Epithelial Cells / drug effects*
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism
  • Fallopian Tubes / drug effects*
  • Fallopian Tubes / immunology
  • Fallopian Tubes / metabolism
  • Female
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • Immunity, Innate / drug effects
  • Interleukin-8 / metabolism
  • Lipopolysaccharides / pharmacology
  • Myxovirus Resistance Proteins
  • Poly I-C / pharmacology*
  • RNA, Messenger / metabolism
  • RNA, Viral / pharmacology
  • Toll-Like Receptor 3 / agonists*
  • Toll-Like Receptor 3 / genetics
  • Toll-Like Receptor 3 / metabolism
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Viruses / immunology*
  • Zymosan / pharmacology
  • beta-Defensins / metabolism
  • eIF-2 Kinase / genetics
  • eIF-2 Kinase / metabolism

Substances

  • DEFB4A protein, human
  • Interleukin-8
  • Lipopolysaccharides
  • Myxovirus Resistance Proteins
  • RNA, Messenger
  • RNA, Viral
  • TLR3 protein, human
  • Toll-Like Receptor 3
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha
  • beta-Defensins
  • Zymosan
  • eIF-2 Kinase
  • OAS1 protein, human
  • 2',5'-Oligoadenylate Synthetase
  • GTP-Binding Proteins
  • Poly I-C