A progesterone-induced blocking factor corrects high resorption rates in mice treated with antiprogesterone

Szekeres-Barthó, Júlia; Chaouat, G.; Kinský, R

doi:10.1016/0002-9378(90)90713-h

Cited by 28 publications

(17 citation statements)

References 12 publications

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“…This dramatic increase may be due to the mediating effect of increased PIBF or a direct effect of dydrogesterone on cytokine production, similar to the effect of progesterone itself as demonstrated by Piccinni (47). It has been highly accepted that progesterone induces the production of Th2 cytokines in vivo and vitro (24,27,28). Szekeres-Bartho and colleagues and the Margni group (48,49) report that progesterone induces the secretion of PIBF through lymphocytes and may be involved in the synthesis of asymmetric Abs.…”

Section: Cd8mentioning

confidence: 99%

“…Data have indicated that a shift of Th1 to Th2 cytokines and suppression of NK cell cytolytic activity may be under the control of an immunomodulatory protein known as progesterone-induced blocking factor (PIBF) 3 (27). PIBF is secreted by T cells, predominantly ␥␦ TCR ϩ and CD8 ϩ (24), upon interaction of progesterone with the progesterone receptors on such cells (28).…”

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confidence: 99%

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Depletion of CD8+ Cells Abolishes the Pregnancy Protective Effect of Progesterone Substitution with Dydrogesterone in Mice by Altering the Th1/Th2 Cytokine Profile

Blois

Joachim

Kandil

et al. 2004

The Journal of Immunology

158

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One of the most remarkable immunological regulations is the maternal immune tolerance toward the fetal semiallograft during pregnancy, which has been referred to as immunity’s pregnant pause. Rejection of the semiallogeneic trophoblast cells must be selectively inhibited and pathways presumably include Th2 cytokines unopposed by Th1 cytokines. Steroid hormones, including progesterone, have similar effects. Low levels of progesterone and Th2 cytokines and high levels of Th1 cytokines are attributable for increased abortions in mammalians, which may be triggered by psychoemotional stress. Thus, the aim of the present study was to provide experimental evidence for the mechanism involved in the mediation of immune responses by endocrine signals during pregnancy and stress-triggered pregnancy failure. DBA/2J-mated CBA/J female mice were randomized in three groups: 1) control females, 2) mice exposed to stress on gestation day 5.5, and 3) mice exposed to stress and substituted with dydrogesterone, a progestogen with a binding profile highly selective for the progesterone receptor on gestation day 5.5. On gestation days 7.5, 9.5, and 10.5, mice of each group were sacrificed, and the frequency of CD8+ cells and cytokine expression (IL-4, IL-12, TNF-α, IFN-γ) in blood and uterus cells was evaluated by flow cytometry. Additionally, some mice were depleted of CD8 cells by injection of mAb. We observed that progesterone substitution abrogated the abortogenic effects of stress exposure by decreasing the frequency of abortogenic cytokines. This pathway was exceedingly CD8-dependent, because depletion of CD8 led to a termination of the pregnancy protective effect of progesterone substitution.

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Section: Cd8mentioning

confidence: 99%

mentioning

confidence: 99%

Depletion of CD8+ Cells Abolishes the Pregnancy Protective Effect of Progesterone Substitution with Dydrogesterone in Mice by Altering the Th1/Th2 Cytokine Profile

Blois

Joachim

Kandil

et al. 2004

The Journal of Immunology

158

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“…The recombinant protein reacts with Abs raised by immunization with the secreted PIBF of lymphocyte origin, suggesting that the recombinant PIBF is related to that, secreted by the lymphocytes (22,23). The recombinant human PIBF proved to be immunologically active, exerting similar effects to PIBF, secreted by pregnancy lymphocytes.…”

Section: Discussionmentioning

confidence: 87%

Molecular Cloning and Immunologic Characterization of a Novel cDNA Coding for Progesterone-Induced Blocking Factor

Polgar

Kispál

Lachmann

et al. 2003

The Journal of Immunology

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Previous studies from our laboratory showed that the immunomodulatory effects of progesterone are mediated by a 34-kDa protein, named the progesterone-induced blocking factor (PIBF). Lymphocytes of women with threatened abortion fail to produce this factor. Via inducing a Th2 biased cytokine production and blocking of NK activity, PIBF prevents induced pregnancy loss in mice, suggesting that substitution therapy with PIBF could be useful as an alternative treatment of certain forms of recurrent spontaneous abortions. Our study was aimed at mapping the sequence and structure of PIBF coding cDNA and characterizing the encoded protein product. Screening of a human liver cDNA library revealed a 2765-bp clone with a 2271-bp open reading frame. The PIBF1 cDNA encodes a protein of 757 amino acid residues with an 89-kDa predicted molecular mass, which shows no significant amino acid sequence homology with any known protein. PIBF produced via recombinant technique is recognized by the Ab specific for the secreted lymphocyte PIBF Ab, and possesses the biological activities of the secreted lymphocyte PIBF. The full-length PIBF is associated with the nucleus, whereas secretion of shorter forms, such a 34-kDa protein is induced by activation of the cell. The 48-kDa N-terminal part of PIBF is biologically active, and the part of the molecule, responsible for modulating NK activity is encoded by exons 2–4. These data provide an initial step for exploiting the possible diagnostic and therapeutic potential of this immunomodulatory molecule.

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“…Furthermore, the treatment of pregnant mice with the progesterone receptor antagonist RU486 leads to an increase in resorption rate and this is associated with the abrogation of C13orf24 production by spleen cells. Since the increase in resorption rate can be reversed by simultaneous administration of C13orf24, this unique factor appears to have an important anti-abortive function in pregnant mice (Szekeres-Bartho et al 1990). The anti-abortive mechanism of C13orf24 is thought to be primarily mediated through its inhibitory effects on NK activity.…”

Section: Progesterone-induced Blocking Factor (C13orf24)mentioning

confidence: 99%

Immunoendocrine aspects of endometrial function and implantation

Lea

Sandra²

2007

Reproduction

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Effective ovarian and uterine function relies on a complex interplay between the endocrine and immune systems. It is generally accepted that in reproductive tissues, oestradiol and progesterone have pro-and anti-inflammatory activities respectively and, in this regard, the paracrine effects of the sex steroids on the ovary are similar to the endocrine effects on the uterus. Ovarian leukocyte recruitment and cytokine release are central to follicle development, ovulation and corpus luteum function. At the uterine level, the cyclical changes in sex steroids regulate the number and distribution of endometrial and decidual immune cells as well as other immune signalling and surveillance factors. The uterine mucosa is unique, in that it must tolerate sperm and the allogeneic blastocyst in a way that does not compromise uterine immune surveillance against bacteria, yeast and viruses. Crosstalk between the sex steroids and immune mediators (systemic and local) are central to these functions, and this article will review these mechanisms and their importance for successful reproductive function and pregnancy success.

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A progesterone-induced blocking factor corrects high resorption rates in mice treated with antiprogesterone

Cited by 28 publications

References 12 publications

Depletion of CD8+ Cells Abolishes the Pregnancy Protective Effect of Progesterone Substitution with Dydrogesterone in Mice by Altering the Th1/Th2 Cytokine Profile

Depletion of CD8+ Cells Abolishes the Pregnancy Protective Effect of Progesterone Substitution with Dydrogesterone in Mice by Altering the Th1/Th2 Cytokine Profile

Molecular Cloning and Immunologic Characterization of a Novel cDNA Coding for Progesterone-Induced Blocking Factor

Immunoendocrine aspects of endometrial function and implantation

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