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.
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.
Authors: H El Costa; H Quillay; R Marlin; C Cannou; M Duriez; F Benjelloun; C de Truchis; M Rahmati; J Ighil; F Barré-Sinoussi; M T Nugeyre; E Menu Journal: Mucosal Immunol Date: 2015-09-09 Impact factor: 7.313
Authors: Irina A Zalenskaya; Theresa Joseph; Jasmin Bavarva; Nazita Yousefieh; Suzanne S Jackson; Titilayo Fashemi; Hidemi S Yamamoto; Robert Settlage; Raina N Fichorova; Gustavo F Doncel Journal: PLoS One Date: 2015-06-08 Impact factor: 3.240
Authors: Jacques Ravel; Pawel Gajer; Li Fu; Christine K Mauck; Sara S K Koenig; Joyce Sakamoto; Alison A Motsinger-Reif; Gustavo F Doncel; Steven L Zeichner Journal: MBio Date: 2012-12-18 Impact factor: 7.867
Authors: Karin Erneholm; Emma Lorenzen; Sarah Bøje; Anja Weinreich Olsen; Peter Andersen; Joseph P Cassidy; Frank Follmann; Henrik E Jensen; Jørgen S Agerholm Journal: BMC Vet Res Date: 2016-09-10 Impact factor: 2.741