Premium
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
Author(s) -
Zalenskaya Irina A.,
Cerocchi Orlando G.,
Joseph Theresa,
Donaghay Melissa A.,
Schriver Suzanne D.,
Doncel Gustavo F.
Publication year - 2011
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/j.1600-0897.2010.00964.x
Subject(s) - microbicide , vaginal microbicide , microbicides for sexually transmitted diseases , downregulation and upregulation , immunology , medicine , immune system , inflammation , biology , population , andrology , human immunodeficiency virus (hiv) , biochemistry , environmental health , gene , health services
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 E 2 (PGE 2 ) 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 PGE 2 , 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.