Estrogen enhances attachment of Chlamydia trachomatis to human endometrial epithelial cells in vitro

Maslow, Arthur S.; Davis, Cralen; Choong, John; Wyrick, Priscilla B.

doi:10.1016/s0002-9378(88)80189-3

Cited by 64 publications

(41 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the studies involving primary human endometrial epithelial cell cultures, it was shown that the concentration of exogenously supplemented estrogen is critical and needs to be similar to concentrations in the normal human physiological range of ca. 10 Ϫ10 M in order to enhance chlamydial infection (17). In the present study, estrogen at this concentration had a less noticeable effect on the rate of infectivity than did a concentration of 10 Ϫ8 M. According to data pertaining to the monitoring of peripheral blood hormonal concentration during the swine estrous cycle, the level of estrogen varies from 10…”

Section: Discussionmentioning

confidence: 48%

“…Subsequently, it was shown that epithelial cells were more sensitive to C. trachomatis serovar E in the estrogen-dominant (proliferative) stage of the human menstrual cycle than at other stages (17,30). When estrogendominant-phase cells were grown and maintained in the normal human physiological concentration of estrogen (10 Ϫ10 M), chlamydial attachment and infectivity was enhanced Ն80%.…”

Section: Discussionmentioning

confidence: 99%

“…HeLa cells (epithelial cells from a cervical adenocarcinoma) have been used for most experimental analyses and are highly sensitive to chlamydial infection, but they are less representative of primary, differentiated target epithelial cells (4). As an alternative to the established transformed cell lines, a few studies have been performed with primary, hormone-responsive polarized human endometrial epithelial cells derived from women undergoing a hysterectomy for benign disease (17,19,29,30). Important information about chlamydial attachment and infection which differed, in several aspects, from data obtained from non-hormone-responsive, nonpolarized, chlamydia-infected HeLa cells was obtained: (i) chlamydial inclusion development in primary human cervical and endometrial epithelial cells was patchy and uneven in distribution; (ii) levels of chlamydial attachment to and infectivity of primary human endometrial epithelial cells were significantly greater in estrogen-dominant than in progesteronedominant cells; (iii) entry of infectious elementary bodies (EBs) into polarized, hormone-responsive, primary human endometrial epithelial cells was mediated predominately by clathrin-coated pit receptor-mediated endocytosis; and (iv) exit of chlamydiae from primary polarized human epithelial cells was pathogenesis directed, i.e., human noninvasive C. trachomatis serovar E progeny exited via the apical surface, whereas invasive C. trachomatis lymphogranuloma venereum-causing progeny were released at the basal domain.…”

mentioning

confidence: 99%

“…This study evaluates the potential for using the C. suis S-45 swine primary genital tract epithelial cell culture model to follow up on previous data obtained from primary human endometrial epithelial cells (17,19,30), especially to study the influence of hormones on chlamydial attachment, adhesionreceptor interactions, and entry and development in genital tract cells, as well as microbicidal efficacy.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Primary Cultures of Female Swine Genital Epithelial Cells In Vitro: a New Approach for the Study of Hormonal Modulation of Chlamydia Infection

et al. 2003

Self Cite

View full text Add to dashboard Cite

Previous studies have demonstrated that female reproductive hormones influence chlamydial infection both in vivo and in vitro. Due to the reduced availability of human genital tissues for research purposes, an alternative hormone-responsive model system was sought to study chlamydial pathogenesis. Mature female swine eliminated from breeding programs were selected as the animals of choice because of the similarity of a sexually transmitted disease syndrome and sequelae in swine to a disease syndrome and sequelae found in humans, because of the near identity of a natural infectious chlamydial isolate from swine to Chlamydia trachomatis serovar D from humans, and because a pig's epithelial cell physiology and the mean length of its estrous cycle are similar to those in humans. Epithelial cells from the cervix, uterus, and horns of the uterus were isolated, cultivated in vitro in Dulbecco's minimum essential medium-Hanks' F-12 (DMEM-F-12) medium with and without exogenous hormone supplementation, and analyzed for Chlamydia suis S-45 infectivity. The distribution of chlamydial inclusions in swine epithelial cells was uneven and was influenced by the genital tract site and hormone status. This study confirmed that, like primary human endometrial epithelial cells, estrogen-dominant swine epithelial cells are more susceptible to chlamydial infection than are progesterone-dominant cells. Further, the more differentiated luminal epithelial cells were more susceptible to infection than were glandular epithelial cells. Interestingly, chlamydial growth in mature luminal epithelia was morphologically more active than in glandular epithelia, where persistent chlamydial forms predominated. Attempts to reprogram epithelial cell physiology and thereby susceptibility to chlamydial infection by reversestage, exogenous hormonal supplementation were unsuccessful. Freshly isolated primary pig epithelial cells frozen at ؊80°C in DMEM-F-12 medium with 10% dimethyl sulfoxide for several weeks can, after thawing, reform characteristic polarized monolayers in 3 to 5 days. Thus, primary swine genital epithelia cultured ex vivo appear to be an excellent cell model for dissecting the hormonal modulation of several aspects of chlamydial pathogenesis and infection.

show abstract

Section: Discussionmentioning

confidence: 48%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Primary Cultures of Female Swine Genital Epithelial Cells In Vitro: a New Approach for the Study of Hormonal Modulation of Chlamydia Infection

et al. 2003

Self Cite

View full text Add to dashboard Cite

show abstract

“…As determined by electron microscopy, the adherent recombinant appeared to be anchored in clathrin-coated pits. Also similar to chlamydial EB, the recombinant E. coli exhibited increased adherence to estrogen-dominant primary endometrial epithelial cells and decreased adherence to progesterone-dominant primary endometrial epithelial cells (31,43). These surprising observations prompted further in-vestigation of the contribution of chlamydial Hsp70 to attachment to human genital epithelial cells.…”

mentioning

confidence: 95%

Surface Accessibility of the 70-KilodaltonChlamydia trachomatisHeat Shock Protein following Reduction of Outer Membrane Protein Disulfide Bonds

et al. 2002

Self Cite

View full text Add to dashboard Cite

Numerous investigations have shown that 70-kDa heat shock protein (Hsp70) homologs interact tightly with hydrophobic proteins and functionally assist proteins in membranous organelles and environments. One such protein is the Chlamydia trachomatis Hsp70 that is associated with isolated outer membrane complexes of infectious elementary bodies (EB). Previous observations have indicated that chlamydial Hsp70 plays a role in EB attachment to, or entry into, endometrial epithelial cells. In this study, immunofluorescence microscopy and transmission electron microscopy observations showed that chlamydial Hsp70 is not a surface-displayed ligand on purified EB. However, brief exposure of EB to the thiol reducing agent dithiothreitol (DTT) led to surface accessibility of the Hsp70 substrate-binding domain. Reduction of the highly disulfide-cross-linked EB outer membrane proteins with DTT resulted in a decrease in EB attachment and infectivity. Interestingly, exposure of EB to the membrane-impermeable thiol-alkylating reagent 5,5-dithiobis(2-nitrobenzoic acid) enhanced attachment but compromised infectivity, suggesting that EB outer membrane proteins must be reduced for entry and productive infection. Together, our data suggest that (i) the structural integrity of the EB outer membrane, maintained by protein disulfide bonds, is important during the initial stages of attachment; (ii) reduction occurs within the localized microenvironment of host cell surfaces once intimate contact is established between EB and host cells; and (iii) subsequent conformational changes in EB ultrastructure allow productive infection in host cells. The accessibility of the Hsp70 substrate-binding domain may support the hypothesis that this protein plays a role in events following the initial stage of attachment instead of serving as a primary, surface-displayed adhesin.A distinguishing feature of the chlamydiae is their transition between infectious elementary bodies (EB) that bind to and enter host cells and noninfectious reticulate bodies that replicate intracellularly within a membrane-bound inclusion. EB are small (diameter, 300 nm) particles with an unusually rigid ultrastructure due to cysteine-rich membrane proteins that exhibit intra-and intermolecular disulfide cross-linking in the envelope (22,36). Several chlamydial molecules, including the cysteine-rich proteins, have been examined to determine their roles in EB attachment to eukaryotic cells (25,26,38,43,46,48,49,50,51). There is evidence that both the 60-kDa cysteinerich membrane protein and the major outer membrane protein (MOMP) serve as receptors for sulfated glycosaminoglycans in a tethering event between EB and host cell surfaces (46,48,49). Adherence mediated by the 40-kDa MOMP appears to be initiated by charge-charge interactions involving surface-exposed domains (50) and a high-mannose oligomannose oligosaccharide (26). It is likely that additional, unidentified surface components also participate in establishing contact between EB and the host cell surface.Although many d...

show abstract

Decreased Risk of Symptomatic Chlamydial Pelvic Inflammatory Disease Associated With Oral Contraceptive Use

Wølner‐Hanssen

Eschenbach

Paavonen

et al. 1990

JAMA

131

View full text Add to dashboard Cite

Estrogen enhances attachment of Chlamydia trachomatis to human endometrial epithelial cells in vitro

Cited by 64 publications

References 15 publications

Primary Cultures of Female Swine Genital Epithelial Cells In Vitro: a New Approach for the Study of Hormonal Modulation of Chlamydia Infection

Primary Cultures of Female Swine Genital Epithelial Cells In Vitro: a New Approach for the Study of Hormonal Modulation of Chlamydia Infection

Surface Accessibility of the 70-KilodaltonChlamydia trachomatisHeat Shock Protein following Reduction of Outer Membrane Protein Disulfide Bonds

Decreased Risk of Symptomatic Chlamydial Pelvic Inflammatory Disease Associated With Oral Contraceptive Use

Contact Info

Product

Resources

About