Induction of cyclooxygenase (COX)-2 in human vaginal epithelial cells in response to TLR ligands and TNF-α

Am J Reprod Immunol. 2012 Jun;67(6):482-90. doi: 10.1111/j.1600-0897.2011.01099.x. Epub 2012 Jan 11.


Problem: Mucosal inflammation caused by infections of the female lower genital tract is considered to be an important cofactor for HIV transmission. We hypothesize that COX-2, a key inflammation-related enzyme, is involved in these responses and is upregulated by microbial ligands and pro-inflammatory cytokines.

Method of study: Human vaginal epithelial cells (VK-2/E6E7) and ectocervical biopsy tissues were stimulated with TLR ligands and the cytokine TNF-α, used as surrogates of vaginal infections, and assessed for COX-2 expression and activity by microarray, real-time RT-PCR, immunoblotting, immunohistochemistry, and ELISA.

Results: TLR agonists and TNF-α induce transcriptional and translational expression of COX-2 in vaginal cells. TLR ligands, MALP2, Pam3CSK4, LTA, and imiquimod induced high epithelial COX-2 expression, while zymosan and poly dI:dC induced very low enzyme expression. Induced mRNA and protein expression correlated with increased COX-2 activity, which led to increased levels of PGE(2) in the cell culture supernatant. These cell-based findings were confirmed in primary cervicovaginal tissue explants.

Conclusion: Induction of COX-2 expression and activity and the consequent increased levels of prostaglandins are common inflammatory pathways in human cervicovaginal epithelial cells and tissues in response to diverse TLR ligands and pro-inflammatory cytokines. These findings are relevant to the understanding of genital mucosal inflammation, its potential treatment, and its possible relationship with increased tissue susceptibility to HIV-1 infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoquinolines / pharmacology
  • Cell Line
  • Cyclooxygenase 2 / biosynthesis*
  • Cyclooxygenase 2 / genetics
  • Dinoprostone / biosynthesis
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Female
  • Humans
  • Imiquimod
  • Ligands
  • Lipopeptides / pharmacology
  • Lipopolysaccharides / pharmacology
  • Polydeoxyribonucleotides / pharmacology
  • RNA, Messenger / biosynthesis
  • Teichoic Acids / pharmacology
  • Toll-Like Receptors / agonists
  • Toll-Like Receptors / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Up-Regulation
  • Vagina / cytology
  • Vagina / metabolism
  • Zymosan / pharmacology


  • Aminoquinolines
  • Ligands
  • Lipopeptides
  • Lipopolysaccharides
  • Pam(3)CSK(4) peptide
  • Polydeoxyribonucleotides
  • RNA, Messenger
  • Teichoic Acids
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha
  • poly d(I-C)
  • lipoteichoic acid
  • Zymosan
  • macrophage stimulatory lipopeptide 2
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Dinoprostone
  • Imiquimod