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

Zalenskaya, Irina A.; Cerocchi, Orlando G.; Joseph, Theresa; Donaghay, Melissa; Schriver, Suzanne D.; Doncel, Gustavo F.

doi:10.1111/j.1600-0897.2010.00964.x

Cited by 20 publications

(23 citation statements)

References 34 publications

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“…Previously, we identified PTGS2 as a biomarker for vaginal inflammation. We have reported the induction of vaginal PTGS2 in response to diverse proinflammatory stimulants, such as TNF-a, microbial ligands, and cell membrane-damaging surfactants [25]. In this study, we demonstrate that SP causes PTGS2 upregulation in human vaginal cells, confirming the inflammatory potential of SP and suggesting a possible role in HIV-1 transmission.…”

Section: Introductionsupporting

confidence: 71%

“…In addition, different MAPKs may also be activated in response to proinflammatory stimuli and engaged in PTGS2 expression [37]. Previously, we have reported that NF-kB and MAPK pathways are involved in PTGS2 expression in vaginal cells in response to the proinflammatory spermicide N-9 [25]. We also found that these pathways are implicated in PTGS2 upregulation via TLRs stimulated by microbial pathogens (unpublished results).…”

Section: Discussionmentioning

confidence: 77%

“…Earlier, we reported that diverse proinflammatory stimuli cause expression of PTGS2 in human vaginal epithelial cells [25,29]. PTGS2 (or COX-2) is an inducible enzyme that is essential in promoting inflammation [32][33][34].…”

Section: Discussionmentioning

confidence: 99%

“…We previously demonstrated that TLR ligands Pam, LTA, and IMQ and the proinflammatory surfactant N-9 induce PTGS2 expression in VK-2 cells [25,29]. In this study, we evaluated the effect of SP on PTGS2 expression in the presence of these compounds.…”

Section: Sp Potentiates Ptgs2 Expression Caused By Tlr Ligands and N-9mentioning

confidence: 96%

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Seminal Plasma Induces Prostaglandin-Endoperoxide Synthase (PTGS) 2 Expression in Immortalized Human Vaginal Cells: Involvement of Semen Prostaglandin E2 in PTGS2 Upregulation1

Joseph

Zalenskaya

Sawyer

et al. 2013

Biology of Reproduction

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Inflammation of the cervicovaginal mucosa is considered a risk factor for HIV infection in heterosexual transmission. In this context, seminal plasma (SP) may play an important role that is not limited to being the main carrier for the virions. It is known that SP induces an inflammatory reaction in the cervix called postcoital leukocytic reaction, which has been associated with promotion of fertility. The mechanisms by which SP triggers this reaction, however, have not been clearly established. Previously we reported the expression of prostaglandin-endoperoxide synthase 2 (PTGS2), also known as cyclooxygenase 2 (COX-2), in human vaginal cells in response to toll-like receptor (TLR) ligands and other proinflammatory stimuli. In this study, we demonstrate that SP induces transcriptional and translational increase of COX-2 expression in human vaginal cells and cervicovaginal tissue explants. Furthermore, SP potentiates vaginal PTGS2 expression induced by other proinflammatory stimulants, such as TLR ligands and a vaginal mucosal irritant (nonoxynol-9) in a synergistic manner. SP-induced PTGS2 expression is mediated by intracellular signaling pathways involving MAPKs and NF-κB. Using fractionation and functional analysis, seminal prostaglandin (PG)-E(2) was identified as a one of the major factors in PTGS2 induction. Given the critical role of this PG-producing enzyme in mucosal inflammatory processes, the finding that SP induces and potentiates the expression of PTGS2 in cervicovaginal cells and tissues has mechanistic implications for the role of SP in fertility-associated mucosal leukocytic reaction and its potential HIV infection-enhancing effect.

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Section: Introductionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Sp Potentiates Ptgs2 Expression Caused By Tlr Ligands and N-9mentioning

confidence: 96%

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Seminal Plasma Induces Prostaglandin-Endoperoxide Synthase (PTGS) 2 Expression in Immortalized Human Vaginal Cells: Involvement of Semen Prostaglandin E2 in PTGS2 Upregulation1

Joseph

Zalenskaya

Sawyer

et al. 2013

Biology of Reproduction

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“…[88][89][90][91] Undesirable properties of the N9 compound are reflective in local vaginal up-regulation of pro-inflammatory COX-2. 92 A newer product, sodium laurel sulfate (the invisible condom), has been found to be safe and well tolerated though its efficacy at preventing HIV transmission remains unclear; 93 ii)Acidifying agents, including Carbopol 974P (BufferGel), Acidform (Amphora), and natural lemon/lime/vinegar douches are also non-specific agents with activity against HIV, HSV-2 and chlamydia by maintaining the naturally acidified milieu of the vagina. While anti-HIV activity has been confirmed in vitro, these agents are cytotoxic to human vaginal cell lines with associated vaginal discharge and ulcerations that may actually serve to facilitate HIV entry.…”

Section: 84mentioning

confidence: 99%

Advances in the Prevention of Heterosexual Transmission of HIV/AIDS Among Women in the United States

Chen

Meyer

Springer

2011

Infectious Disease Reports

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Despite recent advances in testing and treatment, the incidence of HIV/AIDS in the United States has remained stagnant with an estimated 56,300 new infections every year. Women account for an increasing proportion of the epidemic. The vulnerability of women to HIV stems from both increased biologic susceptibility to heterosexual transmission and also the social, economic, and structural disadvantages they often confront. This review describes the main reasons for the increased vulnerability of U.S. women to HIV transmission with particular emphasis on specific highrisk groups including: non-Hispanic blacks, women who use drugs, women with a history of incarceration, and victims of intimate partner violence. Although behavioral approaches to HIV prevention may be effective, pragmatic implementation is often difficult, especially for women who lack sociocultural capital to negotiate condoms with their male partners. Recent advances in HIV prevention show promise in terms of female-initiated interventions. These notably include female condoms, non-specific vaginal microbicides, and antiretroviral oral and vaginal pre-exposure prophylaxis. In this review, we will present evidence in support of these new female-initiated interventions while also emphasizing the importance of advocacy and the political support for these scientific advances to be successful.

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Assessment of topical microbicides to prevent HIV-1 transmission: Concepts, testing, lessons learned

Friend

Kiser

2013

Antiviral Research

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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

Cited by 20 publications

References 34 publications

Seminal Plasma Induces Prostaglandin-Endoperoxide Synthase (PTGS) 2 Expression in Immortalized Human Vaginal Cells: Involvement of Semen Prostaglandin E2 in PTGS2 Upregulation1

Seminal Plasma Induces Prostaglandin-Endoperoxide Synthase (PTGS) 2 Expression in Immortalized Human Vaginal Cells: Involvement of Semen Prostaglandin E2 in PTGS2 Upregulation1

Advances in the Prevention of Heterosexual Transmission of HIV/AIDS Among Women in the United States

Assessment of topical microbicides to prevent HIV-1 transmission: Concepts, testing, lessons learned

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