Current address: Hospital Zonal Bariloche, (8400)Bariloche, Rio Negro, Republica Argentina.
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ORIGINAL ARTICLE
Increased COX-2 Expression in Human Vaginal Epithelial Cells Exposed to Nonoxynol-9, a Vaginal Contraceptive Microbicide that Failed to Protect Women from HIV-1 Infection
Article first published online: 18 JAN 2011
DOI: 10.1111/j.1600-0897.2010.00964.x
© 2011 John Wiley & Sons A/S
Additional Information
How to Cite
Zalenskaya, I. A., Cerocchi, O. G., Joseph, T., Donaghay, M. A., Schriver, S. D. and Doncel, G. F. (2011), Increased COX-2 Expression in Human Vaginal Epithelial Cells Exposed to Nonoxynol-9, a Vaginal Contraceptive Microbicide that Failed to Protect Women from HIV-1 Infection. American Journal of Reproductive Immunology, 65: 569–577. doi: 10.1111/j.1600-0897.2010.00964.x
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Current address: Hospital Zonal Bariloche, (8400)Bariloche, Rio Negro, Republica Argentina.
Publication History
- Issue published online: 25 APR 2011
- Article first published online: 18 JAN 2011
- Submitted September 20, 2010; accepted December 6, 2010.
Keywords:
- cyclooxygenase-2;
- inflammation biomarkers;
- microbicides;
- nonoxynol-9;
- PGE2;
- vaginal epithelium
Citation Zalenskaya IA, Cerocchi OG, Joseph T, Donaghay MA, Schriver SD, Doncel GF. Increased COX-2 expression in human vaginal epithelial cells exposed to nonoxynol-9, a vaginal contraceptive microbicide that failed to protect women from HIV-1 infection. Am J Reprod Immunol 2011; 65: 569–577
Problem Despite displaying virucidal activity in vitro, nonoxynol-9 (N-9), a vaginal contraceptive microbicide candidate, failed to reduce the rate of human immunodeficiency virus (HIV) transmission in clinical trials. With frequent use, it even increased the risk of HIV acquisition. Such outcome was postulated to be because of N-9-induced mucosal inflammation, which resulted in recruitment of HIV-target immune cells to the sites of virus entry. Understanding the mechanism underlying the response of the vaginal epithelium to N-9 is critical to properly evaluate the safety of prospective vaginal microbicides and contraceptives.
Methods and results Using DNA microarray and quantitative RT-PCR techniques, we observed that N-9 initiated a strong transcriptional upregulation of cyclooxygenase-2 (COX-2) in immortalized human vaginal epithelial cells (VK2/E6E7 cell line). Increased COX-2 protein expression evaluated by immunoblotting was dose- and time-dependent. The level of prostaglandin E2 (PGE2) increased subsequently to COX-2 elevation. This upregulation was in part because of NF-kB activation.
Conclusion Expression of COX-2, a potent inflammation-related enzyme, as well as increased secretion of PGE2, an important local mediator of mucosal immunoinflammatory responses, by human vaginal epithelial cells exposed to vaginal microbicide and contraceptive candidates may be used as a biomarker of undesirable compound properties.