Neisseria gonorrhoeae Challenge Increases Matrix Metalloproteinase-8 Expression in Fallopian Tube Explants

Juica, Natalia; Rodas, Paula I.; Solar, Paula; Borda, Paula; Vargas, Renato; Muñoz, C.; Paredes, Rodolfo; Christodoulides, Myron; Velásquez, Luís

doi:10.3389/fcimb.2017.00399

Cited by 6 publications

(3 citation statements)

References 46 publications

(45 reference statements)

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“…ROS could trigger the tissue MMP activation and subsequent ECM degradation in the process of human trophoblast invasion [ 34 ] or rupture of fetal membranes, a major cause of preterm birth [ 35 ]. Previous studies have also indicated that MMP3, MMP-9, and TIMP-1 might participate in oviduct remodeling during the menstrual cycle [ 36 ], whereas MMP-8 activity participates in tissue remodeling processes during inflammation to establish successful Gonorrhea infection [ 37 ]. From this perspective, it is not surprising that we found GPx8, a member of the antioxidant enzyme family that degrades H 2 O 2 , in the ECM of the rat oviduct and uterus.…”

Section: Discussionmentioning

confidence: 99%

GPx8 Expression in Rat Oocytes, Embryos, and Female Genital Organs During Preimplantation Period of Pregnancy

Mihálik

Kreheľová

Kovaříková

et al. 2020

IJMS

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This study aimed to detect the presence of glutathione peroxidase 8 (GPx8) in rat during preimplantation period of pregnancy. Females were killed on first (D1), third (D3), and fifth (D5) day of pregnancy. The presence of GPx8 in embryos was detected under the confocal microscope, the presence of GPx8 in genital organs was confirmed immunohistochemically, and the amount of GPx8 was determined using densitometry. We found that GPx8 is dispersed in the cytoplasm of oocytes, while after fertilization, it is concentrated in granules. From 4-cell stage till blastocyst, GPx8 reaction was found in the perinuclear region. In the ovary, GPx8 was seen in granulosa-lutein cells, in plasma of blood vessels, and inside Graafian follicles. In oviduct, GPx8 was detected in the plasma and in the extracellular matrix (ECM). Moreover, epithelial cells of isthmus were positive. In uterus, GPx8 was observed in the uterine glands, in the plasma, and in ECM. On D5, the enzyme disappeared from the uterine glands and appeared in fibroblasts. Densitometry revealed that the highest amount of GPx8 was on D1 and subsequently declined. To our knowledge, this is the first paper describing GPx8 presence in the oocytes, preimplantation embryos, and female genital organs in mammals. Our results improve the understanding of antioxidant enzymes presence during pregnancy in defense against oxidative stress, which is considered to be one of the main causes of infertility.

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Section: Discussionmentioning

confidence: 99%

GPx8 Expression in Rat Oocytes, Embryos, and Female Genital Organs During Preimplantation Period of Pregnancy

Mihálik

Kreheľová

Kovaříková

et al. 2020

IJMS

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“…NOD agonists promoted downregulation of ADAMTSL4. Other groups have observed MMP-2, -8, and -9 upregulation following N. gonorrhoeae challenge of Fallopian tube epithelia (119,120). In contrast, only MMP-2 and -9 are implicated in C. trachomatis mediated Fallopian tube damage.…”

Section: Discussionmentioning

confidence: 94%

IL-17C is a driver of damaging inflammation duringNeisseria gonorrhoeaeinfection of human Fallopian tube

Garcia

Lenz

Hackett

et al. 2022

Preprint

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The human-restricted pathogen Neisseria gonorrhoeae ascends into the upper female reproductive tract to cause damaging inflammation within the Fallopian tubes (salpingitis) and pelvic inflammatory disease (PID), increasing the risk of infertility and life-threatening ectopic pregnancy. The loss of ciliated cells from the epithelium is thought to be both a consequence of inflammation and a cause of the associated adverse sequelae. However, the links between infection, inflammation, and ciliated cell extrusion remain unresolved. With the use of ex vivo cultures of human Fallopian tube paired with RNA sequencing we defined the tissue response to gonococcal challenge, identifying cytokine, chemokine, cell adhesion, and apoptosis related transcripts not previously recognized as potentiators of gonococcal PID. Unexpectedly, the cytokine IL-17C was one of the most highly induced genes. Yet, this cytokine has no previous association with gonococcal disease nor any sexually transmitted infection and thus it was selected for further characterization in our model. We show that human Fallopian tubes express the IL-17C receptor (IL-17RE) on the epithelial surface and that treatment with purified IL-17C induces pro-inflammatory cytokine secretion in addition to sloughing of the epithelium and generalized tissue damage. These results demonstrate a previously unrecognized but critical role of IL-17C in the damaging inflammation induced by gonococci in a human explant model of PID.

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“…During gonococcal infection of fallopian tube epithelial cells, MMP2 accumulates intracellularly while MMP9 secretion is increased (MMP3 and MMP8 levels are unchanged) ( 58 ). In fallopian tube explants, MMP8 expression is increased following GC infection, while transcription of MMP3 and MMP9 (as well as the TIMP metallopeptidase inhibitor 1, TIMP-1) are unchanged ( 59 ). The functions and localization of MMPs, when coupled with data indicating their induction during fallopian tube infection, makes these enzymes prime candidates for mechanistic involvement in epithelial damage.…”

Section: Invading the Fallopian Tubementioning

confidence: 99%

Pathogenesis of Neisseria gonorrhoeae and the Host Defense in Ascending Infections of Human Fallopian Tube

Lenz

Dillard

2018

Front. Immunol.

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Neisseria gonorrhoeae is an obligate human pathogen that causes mucosal surface infections of male and female reproductive tracts, pharynx, rectum, and conjunctiva. Asymptomatic or unnoticed infections in the lower reproductive tract of women can lead to serious, long-term consequences if these infections ascend into the fallopian tube. The damage caused by gonococcal infection and the subsequent inflammatory response produce the condition known as pelvic inflammatory disease (PID). Infection can lead to tubal scarring, occlusion of the oviduct, and loss of critical ciliated cells. Consequences of the damage sustained on the fallopian tube epithelium include increased risk of ectopic pregnancy and tubal-factor infertility. Additionally, the resolution of infection can produce new adhesions between internal tissues, which can tear and reform, producing chronic pelvic pain. As a bacterium adapted to life in a human host, the gonococcus presents a challenge to the development of model systems for probing host-microbe interactions. Advances in small-animal models have yielded previously unattainable data on systemic immune responses, but the specificity of N. gonorrhoeae for many known (and unknown) host targets remains a constant hurdle. Infections of human volunteers are possible, though they present ethical and logistical challenges, and are necessarily limited to males due to the risk of severe complications in women. It is routine, however, that normal, healthy fallopian tubes are removed in the course of different gynecological surgeries (namely hysterectomy), making the very tissue most consequentially damaged during ascending gonococcal infection available for laboratory research. The study of fallopian tube organ cultures has allowed the opportunity to observe gonococcal biology and immune responses in a complex, multi-layered tissue from a natural host. Forty-five years since the first published example of human fallopian tube being infected ex vivo with N. gonorrhoeae, we review what modeling infections in human tissue explants has taught us about the gonococcus, what we have learned about the defenses mounted by the human host in the upper female reproductive tract, what other fields have taught us about ciliated and non-ciliated cell development, and ultimately offer suggestions regarding the next generation of model systems to help expand our ability to study gonococcal pathogenesis.

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Neisseria gonorrhoeae Challenge Increases Matrix Metalloproteinase-8 Expression in Fallopian Tube Explants

Cited by 6 publications

References 46 publications

GPx8 Expression in Rat Oocytes, Embryos, and Female Genital Organs During Preimplantation Period of Pregnancy

GPx8 Expression in Rat Oocytes, Embryos, and Female Genital Organs During Preimplantation Period of Pregnancy

IL-17C is a driver of damaging inflammation duringNeisseria gonorrhoeaeinfection of human Fallopian tube

Pathogenesis of Neisseria gonorrhoeae and the Host Defense in Ascending Infections of Human Fallopian Tube

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