Induction of Cyclooxygenase (COX)-2 in Human Vaginal Epithelial Cells in Response to TLR ligands and TNF-α
Version of Record online: 11 JAN 2012
© 2012 John Wiley & Sons A/S
American Journal of Reproductive Immunology
Volume 67, Issue 6, pages 482–490, June 2012
How to Cite
Joseph T, Zalenskaya IA, Yousefieh N, Schriver SD, Cote LC, Chandra N, Doncel GF. Induction of cyclooxygenase (COX)-2 in human vaginal epithelial cells in response to TLR ligands and TNF-α. Am J Reprod Immunol 2012; 67: 482–490
- Issue online: 10 MAY 2012
- Version of Record online: 11 JAN 2012
- Manuscript Accepted: 8 DEC 2011
- Manuscript Received: 2 JUL 2011
- International Development. Grant Number: GPO-8-00-08-00005-00
- Bill and Melinda Gates Foundation. Grant Number: 41266
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.
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 PGE2 in the cell culture supernatant. These cell-based findings were confirmed in primary cervicovaginal tissue explants.
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.