Antiproliferative Effect of Interferon-γ in Human Endometrial Epithelial Cells in Vitro: Potential Local Growth Modulatory Role in Endometrium*

Tabibzadeh, Siamak; Satyaswaroop, P.G.; Rao, Potu N.

doi:10.1210/jcem-67-1-131

Cited by 74 publications

(31 citation statements)

References 21 publications

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“…Less immunohistochemical staining was observed in the proliferative phase, but as the men strual cycle progressed, more staining was observed, with the most IFN-y observed in the late secretory phase. This general increase in IFN-y throughout the normal men strual cycle may reflect the progressively increasing in flammatory state of the endometrium prior to normal menstruation and provides anatomical evidence for the hypothesis that IFN-y is involved in endometrial remod eling [18].…”

Section: Discussionmentioning

confidence: 70%

“…Immunohistochemical studies have demonstrated macrophages and T cells in ectopic endo metrium (endometriosis) [6] and mRNA for IFN-y [7], Elevated numbers of macrophages and lymphocytes, and elevated cytokine levels have been reported in peritoneal fluid from women with endometriosis compared to those without disease [8][9][10][11][12][13][14], IFN-y, primarily secreted by acti vated T cells [15], differentially induces expression of the immune activation, antigen presentation marker, HLA-DR, on activated T cells and endometrial epithelium [ 16,17] and has been proposed to be involved in endometrial remodeling by inhibiting endometrial growth [ 18]. IFN-y has also been reported to adversely effect in vitro sperm motion parameters [ 19], fertilization [20], embryo devel opment [20], implantation events [21], and trophoblast proliferation [22], and may be responsible for the repro ductive failure of many women with recurrent sponta neous abortion [23].…”

Section: Introductionmentioning

confidence: 99%

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Localization of T Cells, Interferon-Gamma and HLA-DR in Eutopic and Ectopic Human Endometrium

Chiang

Hill

1997

Gynecol Obstet Invest

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Objectives: Immunologic mechanisms are implicated in the pathogenesis of endometriosis and endometriosis-associated reproductive failure. The purpose of this study was to describe key immune response elements in eutopic and ectopic endometrium and to test the hypothesis that expression of CD3-positive T cells, the T-helper 1-type cytokine, IFN-g, and the antigen presentation marker, HLA-DR, vary throughout the menstrual cycle in eutopic endometrium and are more abundantly expressed in ectopic than in eutopic endometrium. Methods: Eutopic and ectopic endometrium obtained at hysterectomy from 7 women with endometriosis were compared with hysterectomy specimens from 7 women with adenomyosis and 10 women without endometriosis or endometrial pathology. Tissues were formalin-fixed, paraffin-embedded, sectioned and stained using the biotin-streptavidin-alkaline phosphatase technique and antibodies to human CD3, IFN-g, and HLA-DR. Eutopic endometrial samples were histologically divided into menses (n = 5), proliferative (n = 9), and secretory (n = 10) phases. Positive control tissues (spleen) and negative controls (no primary antibody) were used in each experiment. Results: T cells, IFN-g and HLA-DR-positive cells were observed in eutopic endometrial samples throughout the menstrual cycle. Glandular epithelium was CD3-negative except for CD3-positive cells surrounding and occasionally interdigitating between glandular epithelium. Glandular epithelium was IFN-g-positive and HLA-DR-positive in all phases except the proliferative phase. Staining was more often observed in the basalis than in the functionalis layer, ranging from patchy staining to the entire gland. T cells, IFN-g, and HLA-DR-positive stromal cells were more abundant in secretory endometrium than in proliferative samples. CD3, IFN-g, and HLA-DR-positive cells were scattered throughout the myometrium and concentrated in vessels. Higher intensity staining was observed in ectopic than in eutopic endometrium, with CD3 and HLA-DR-positive cells forming aggregates around IFN-g and HLA-DR-positive glands. The intensity of IFN-g staining in ectopic endometrium was similar to the intensity of staining observed in menstrual and late secretory basalis samples from eutopic endometrium. Conclusions: The results of this observational study suggest that activated T cells, IFN-g and upregulation of antigen presentation may play a role in normal endometrial physiology. The increased number of T cells, expression of IFN-g and enhanced antigen presentation in ectopic compared to eutopic endometrium support the concept that cellular immune activation is involved in endometriosis and its sequelae.

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Section: Discussionmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Localization of T Cells, Interferon-Gamma and HLA-DR in Eutopic and Ectopic Human Endometrium

Chiang

Hill

1997

Gynecol Obstet Invest

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“…12,13 Its role in endometriosis is unclear. However, although IFN-c is known to inhibit the proliferation of human endometrial epithelium, 14 the resistance of endometriotic cells to IFN-c-induced cell growth inhibition and apoptosis has been found to be a possible mechanism involved in the pathogenesis of endometriosis. 15 In addition, many studies have shown that the concentration of IFN-c is decreased in the peritoneal fluid of patients with endometriosis, 6,15,16 although results suggesting that the concentration does not differ between patients with endometriosis and controls have also been reported.…”

Section: Introductionmentioning

confidence: 99%

Association of the interferon-γ gene (CA)n repeat polymorphism with endometriosis

Kim

Choi

Hwang

et al. 2011

BJOG: An International Journal of Obstetrics &Amp; Gynaecology

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“…necessary for implantation. In several experimental models, it was shown that IFN-γ increases the endometrial epithelial barrier permeability of the basolateral surface and inhibits the proliferation of human endometrial cells [73,75]. IFN-γ expressed and secreted by T cells and lymphoid aggregates induces the human leukocyte antigen DR (HLA-DR) adjacent to the endometrial epithelium, which supports a role of IFN-γ in the induction of lympho-epithelial interactions [74].…”

Section: Possible Role In Conceptus Implantationmentioning

confidence: 97%

Trophoblastic interferon-gamma: current knowledge and possible role(s) in early pig pregnancy

Cencič

Bonnardière

2002

Vet. Res.

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-In the pig as in ruminant species, the implantation of the elongated conceptus -the embryo with its associated membranes -onto the maternal uterus is accompanied by an intense secretion of interferon (IFN), which culminates at day 15 of development. It has been shown that in fact the pig trophectoderm -the polarized epithelium which lines the conceptus -simultaneously secretes two types of interferons: IFN-gamma (IFN-γ ), which is the more abundant species, is produced in very substantial amounts. Another IFN is also secreted, which happens to be a novel type I IFN, now named IFN-δ. It was previously shown that the uterus is the most probable target of the pig trophoblastic IFNs, since no autocrine effect was found on the trophoblast. It has also been shown that, unlike for the ruminant species, the pig trophoblastic IFNs do not play an apparent role in the so-called maternal recognition of pregnancy. We have focused this review on IFN-γ , because first, it is the major species secreted and secondly, IFN-γ has various regulatory effects on different tissues, including lymphoid cells. We particularly address the question of the possible role of trophoblastic IFN-γ in early pregnancy, in the light of the known biological functions of human and mouse IFN-γ .interferon-gamma / embryo / trophoblast / pig / implantation Résumé -Interféron-gamma trophoblastique : état actuel des connaissances et rôle(s) possible(s) en début de gestation chez le porc. Chez le porc, comme chez les ruminants, l'implantation du conceptus (l'embryon et ses membranes annexes) dans l'utérus maternel s'accompagne d'une intense sécrétion d'interféron (IFN), laquelle culmine au 15 e jour du développement. On a montré que le trophectoderme -l'épithélium polarisé qui borde le conceptus -sécrète simultanément deux types d'IFN : l'IFN-gamma, qui est le plus abondant, est produit en très grande quantité. L'autre interféron, apparenté aux IFN de type I, s'avère être une nouvelle espèce, nommée IFN-δ. Des résultats antérieurs ont montré que l'utérus est la cible la plus probable des interférons trophoblastiques, puisqu'aucun effet autocrine 139 Vet. Res. 33 (2002) 139-157

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Antiproliferative Effect of Interferon-γ in Human Endometrial Epithelial Cells in Vitro: Potential Local Growth Modulatory Role in Endometrium*

Cited by 74 publications

References 21 publications

Localization of T Cells, Interferon-Gamma and HLA-DR in Eutopic and Ectopic Human Endometrium

Localization of T Cells, Interferon-Gamma and HLA-DR in Eutopic and Ectopic Human Endometrium

Association of the interferon-γ gene (CA)n repeat polymorphism with endometriosis

Trophoblastic interferon-gamma: current knowledge and possible role(s) in early pig pregnancy

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