Induction of Cyclooxygenase (<scp>COX</scp>)‐2 in Human Vaginal Epithelial Cells in Response to <scp>TLR</scp> ligands and <scp>TNF</scp>‐α

Joseph, Theresa; Zalenskaya, Irina A.; Yousefieh, Nazita; Schriver, Suzanne D.; Cote, Lyn C.; Chandra, Neelima; Doncel, Gustavo F.

doi:10.1111/j.1600-0897.2011.01099.x

Cited by 18 publications

(16 citation statements)

References 41 publications

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“…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%

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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: 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%

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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“…In the FGT, mild inflammatory responses are observed, possibly due to an intrinsic bias of this tissue to exposure to large numbers of commensals. TLR-dependent stimulation of FGT epithelial cells in vitro induces secretion of IL-1α, IL-1β, IL-6, IL-8 and TNF-α (64, 174), and cyclooxygenase 2 (COX-2), an inducible enzyme associated with mucosal inflammation (131), but few studies exist to support these findings in vivo . During infection by sexually transmitted pathogens, such as Chlamydia or Neisseria gonorrhoeae , secretion of IFN-γ, IL-10, IL-12, IL-1β, IL-6, and IL-8 has been reported in the cervix, fallopian tubes, and cervical secretions (174, 175).…”

Section: Tlr Expression and Responses In Human Mucosal Epithelial Tismentioning

confidence: 99%

TLR-Dependent Human Mucosal Epithelial Cell Responses to Microbial Pathogens

2014

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Toll-like receptor (TLR) signaling represents one of the best studied pathways to implement defense mechanisms against invading microbes in human being as well as in animals. TLRs respond to specific microbial ligands and to danger signals produced by the host during infection, and initiate downstream cascades that activate both innate and adaptive immunity. TLRs are expressed by professional immune cells and by the large majority of non-hematopoietic cells, including epithelial cells. In epithelial tissues, TLR functions are particularly important because these sites are constantly exposed to microorganisms, due to their location at the host interface with the environment. While at these sites specific defense mechanisms and inflammatory responses are initiated via TLR signaling against pathogens, suppression or lack of TLR activation is also observed in response to the commensal microbiota. The mechanisms by which TLR signaling is regulated in mucosal epithelial cells include differential expression and levels of TLRs (and their signaling partners), their cellular localization and positioning within the tissue in a fashion that favors responses to pathogens while dampening responses to commensals and maintaining tissue homeostasis in physiologic conditions. In this review, the expression and activation of TLRs in mucosal epithelial cells of several sites of the human body are examined. Specifically, the oral cavity, the ear canal and eye, the airways, the gut, and the reproductive tract are discussed, along with how site-specific host defense mechanisms are implemented via TLR signaling.

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“…The characterization included immunohistochemical staining of cyclooxygenase-2 (cox-2), a key enzyme for prostaglandin synthesis in the early inflammatory response in both pigs and humans, and interleukin-8 (IL-8), which has a similar function as proinflammatory cytokine and neutrophil chemoattractant in both pigs and humans, and is additionally known to be upregulated following C. trachomatis infection [23–26]. …”

Section: Introductionmentioning

confidence: 99%

Genital tract lesions in sexually mature Göttingen minipigs during the initial stages of experimental vaginal infection with Chlamydia trachomatis serovar D

et al. 2016

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BackgroundChlamydia is one of the most common sexually transmitted diseases in humans worldwide, causing chronic lesions in the reproductive tract. Due to its often asymptomatic course, there is limited knowledge about the initial changes in the genital tract following infection. This study employs a novel sexually mature minipig model to investigate the initial histopathological changes following vaginal infection with Chlamydia trachomatis serovar D.ResultsA vaginal inoculation resulted in an infection primarily affecting the lower genital tract. The histopathological changes were characterized by a subepithelial inflammation consisting of neutrophils and mononuclear cells, followed by an increase in the number of plasma cells within the sub-epithelial stroma of the vagina. Detection of Chlamydia was associated with expression of cyclooxygenase-2 and interleukin-8 by superficial epithelial cells. The infection was self-limiting, with a duration of 7 days.ConclusionNeutrophils, plasma cells and IL-8 have been linked with Chlamydia genital infection of unknown duration in human patients. In this study, we observe a similar pattern of local immune response/inflammation following experimental inoculation suggesting this porcine model shows promise as a model for translational chlamydia research.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-016-0793-6) contains supplementary material, which is available to authorized users.

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Induction of Cyclooxygenase (COX)‐2 in Human Vaginal Epithelial Cells in Response to TLR ligands and TNF‐α

Cited by 18 publications

References 41 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

TLR-Dependent Human Mucosal Epithelial Cell Responses to Microbial Pathogens

Genital tract lesions in sexually mature Göttingen minipigs during the initial stages of experimental vaginal infection with Chlamydia trachomatis serovar D

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