Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 82
Filter
Add more filters










Publication year range
1.
Biochemistry (Mosc) ; 85(8): 839-853, 2020 Aug.
Article in English | MEDLINE | ID: mdl-33045946

ABSTRACT

The work is focused on physiological role of the hormone kisspeptin produced by neurons of the hypothalamus anterior zone, which is a key regulator of reproduction processes. Role of the hormone in transmission of information on metabolic activity and induction of the secretion of gonadotropin-releasing hormone (GnRH) by the hypothalamus that determines gestation processes involving fertilization, placentation, fetal development, and child birth is considered. The literature data on molecular mechanisms and effects of kisspeptin on reproductive system including puberty initiation are summarized and analyzed. In addition, attention is paid to hormone-mediated changes in the cardiovascular system in pregnant women. For the first time, the review examines the effect of kisspeptin on functional activity of immune system cells presenting molecular mechanisms of the hormone signal transduction on the level of lymphoid cells that lead to the immune tolerance induction. In conclusion, a conceptual model is presented that determines the role of kisspeptin as an integrator of reproductive and immune functions during pregnancy.


Subject(s)
Immune Tolerance , Kisspeptins/metabolism , Reproduction/immunology , Animals , Female , Genes, Tumor Suppressor , Gonadotropin-Releasing Hormone/metabolism , Humans , Hypothalamo-Hypophyseal System/metabolism , Hypothalamus/metabolism , Kisspeptins/genetics , Neurons/metabolism , Pregnancy , Receptors, Kisspeptin-1/genetics , Receptors, Kisspeptin-1/metabolism
2.
Biochemistry (Mosc) ; 84(9): 992-1007, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31693459

ABSTRACT

The review discusses the mechanisms of participation of natural killer T cells (NKT cells) in the induction of antiphospholipid antibodies (APA) that play a major pathogenetic role in the formation of antiphospholipid syndrome (APS), summarizes the data on APS pathogenesis, and presents modern concepts on the antibody formation involving follicular helper type II NK cells.


Subject(s)
Antiphospholipid Syndrome/immunology , Natural Killer T-Cells/immunology , Animals , Antibodies, Antiphospholipid/immunology , Humans
3.
Bull Exp Biol Med ; 167(1): 57-61, 2019 May.
Article in English | MEDLINE | ID: mdl-31177451

ABSTRACT

We studied the effect of estriol, chorionic gonadotropin, oncostatin M, and hormone-cytokine combinations on the expression of recombinase RAG-1 in T-regulatory (Treg) and T helper 17 (Th17) lymphocytes. It was found that estriol in a concentration corresponding to the first trimester of pregnancy increased the level of Treg (CD4+FoxP3+) cells and suppressed the formation of Th17 (CD4+RORC+) lymphocytes. This effect was nor observed after individual administration of chorionic gonadotropin and oncostatin M, but some combinations of the studied hormones with oncostatin M increased the percentage of CD4+FOXP3+ cells. In the presence of oncostatin M, the studied hormones enhanced the expression of RAG-1 in CD4+FoxP3+ cells, but not in CD4+RORC+ cells, thereby initiating of Treg T-cell receptor (TCR) revision. The mechanisms of hormone cytokine control of induction of the immune tolerance during pregnancy are discussed.


Subject(s)
Chorionic Gonadotropin/pharmacology , Estriol/pharmacology , Oncostatin M/pharmacology , Recombinases/metabolism , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/enzymology , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/metabolism , Cells, Cultured , Female , Forkhead Transcription Factors/metabolism , Humans
4.
Dokl Biochem Biophys ; 484(1): 73-77, 2019 May.
Article in English | MEDLINE | ID: mdl-31012019

ABSTRACT

The effect of estradiol (E2), progesterone (P4), and oncostatin M (OSM) on the differentiation of CD4+ T cells to T regulatory (Treg) lymphocytes and T helpers 17 (Th17) was investigated. The possibility of revision of the T cell receptor in these subpopulations by evaluating the expression of RAG-1 recombinase was also studied. E2 at concentrations characteristic of pregnancy trimester I, but no P4 or OSM, increased the Treg level. Combination of sex steroids with OSM increased the percent of CD4+FOXP3+ cells and enhanced RAG-1 expression in these cells, thus promoting the development of immune tolerance during pregnancy. In the study of Th17, such effect of the hormones and OSM was not detected.


Subject(s)
Estradiol/pharmacology , Gene Expression Regulation, Enzymologic/drug effects , Homeodomain Proteins/biosynthesis , Oncostatin M/pharmacology , Progesterone/pharmacology , T-Lymphocytes, Regulatory/enzymology , Th17 Cells/enzymology , Adult , Female , Humans , Pregnancy
5.
Biochemistry (Mosc) ; 84(1): 1-10, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30927520

ABSTRACT

Molecular mechanisms of the immunomodulatory effects of leptin and ghrelin in concentrations typical for pregnancy on the maturation and functional activity of dendritic cells (DCs) generated from the peripheral blood monocytes of women are investigated. The presence of leptin during DC maturation did not affect the levels of CD83+CD1c+, CD86+CD1c+, and HLA-DR+CD1c+ DCs, but increased the amount and the activity of the enzyme indoleamine 2,3-dioxygenase (IDO). Cell culturing in the presence of ghrelin or combination of leptin and ghrelin reduced the percentage of CD86+CD1c+ DCs but did not affect the levels of CD83+CD1c+ and HLA-DR+CD1c+ DCs. In addition, ghrelin reduced the number of IDO molecules without affecting its activity. Simultaneous presence of leptin and ghrelin increased induced IDO activity without affecting the amount of the enzyme in DCs. The effects of leptin and ghrelin on the investigated functions of DCs in some cases correlated with high levels of cAMP. New mechanisms for leptin and ghrelin regulation of tolerogenic functions of DCs in pregnancy are proposed.


Subject(s)
Dendritic Cells/drug effects , Ghrelin/pharmacology , Leptin/pharmacology , Adult , Antigens, CD/analysis , Cyclic AMP/analysis , Dendritic Cells/cytology , Female , Humans , Immunologic Factors/pharmacology , Indoleamine-Pyrrole 2,3,-Dioxygenase/analysis , Monocytes/cytology , Pregnancy , Young Adult
6.
Bull Exp Biol Med ; 165(2): 230-234, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29922998

ABSTRACT

We studied the effect of hormones estriol, ghrelin, kisspeptin, and chorionic gonadotropin in concentrations corresponding to their content in the peripheral blood in each trimester of pregnancy on the expression of membrane molecules on myeloid and plasmacytoid dendritic cells of the thymus. It was found that thymic myeloid dendritic cells are sensitive to the action of estriol and kisspeptin. Estriol in a concentration of the first trimester of pregnancy reduces the number of myeloid dendritic cells expressing receptor for thymic stromal lymphopoietin (CD11c+TSLP-R+) and inhibitory molecule B7-H3 (CD11c+CD276+). In contrast to estriol, kisspeptin regulates the processes of differentiation of thymic myeloid dendritic cells in concentrations typical of the second-third trimesters and reduced their total number (CD11c+) and the number of cells expressing TSLP-R (CD11c+TSLP-R+). Estriol and kisspeptin do not affect the total number of plasmacytoid dendritic cells (CD303+) and expression of TSLP-R and CD276 by these cells. Ghrelin and chorionic gonadotropin in the studied concentrations had no significant effect on the total number of thymic myeloid and plasmacytoid dendritic cells and on the expression of membrane molecules of TSLP-R and CD276.


Subject(s)
Cell Differentiation/drug effects , Dendritic Cells/drug effects , Hormones/pharmacology , Thymus Gland/cytology , Cells, Cultured , Chorionic Gonadotropin/blood , Chorionic Gonadotropin/pharmacology , Dendritic Cells/physiology , Estriol/blood , Estriol/pharmacology , Female , Ghrelin/blood , Ghrelin/pharmacology , Hematopoiesis/drug effects , Hormones/blood , Humans , Infant , Infant, Newborn , Kisspeptins/blood , Kisspeptins/pharmacology , Maternal-Fetal Exchange/physiology , Pregnancy/blood , Primary Cell Culture , Thymocytes/cytology , Thymocytes/drug effects , Thymocytes/physiology , Thymus Gland/drug effects
7.
Biochemistry (Mosc) ; 82(9): 1061-1072, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28988536

ABSTRACT

The role of phosphatidylinositol-3 kinase (PI3K) and protein kinase A (PKA) in leptin and ghrelin regulation of formation of adaptive (a) subpopulations of CD4+ T-lymphocytes (helper (h) cells producing interleukin-17A) (aTÒ»17) and of T-regulatory lymphocytes (aTreg) in the context of physiological pregnancy is established. It is shown that leptin at a concentration typical for the second half of pregnancy (trimesters II-III) enhances the differentiation of aTÒ»17 with a high level of interleukin-17A (IL-17A) production and the expression of the chemokine receptor CCR6 with the participation of PI3K. Simultaneously, leptin reduces formation of aTreg expressing the suppressor molecule CTLA-4, which determines the function of these cells. Ghrelin at a concentration characteristic of the first half of pregnancy (trimesters I-II), in contrast, enhances aTreg formation and, in parallel, reduces the level aTÒ»17 (that express CCR6) and the IL-17A production by aTh17. PKA, likewise PI3K, participates in regulatory effects of ghrelin on the formation of aTÒ»17 and aTreg. The combined action of leptin and ghrelin (via PKA participation) enhances formation of only aTreg, which determines the priority of this molecular mechanism and explains why the investigated hormones with reciprocal differentiating potential do not come into antagonism at the level of immune system cells during pregnancy.


Subject(s)
Cyclic AMP-Dependent Protein Kinases/physiology , Ghrelin/physiology , Leptin/physiology , Phosphatidylinositol 3-Kinase/physiology , T-Lymphocytes, Regulatory/immunology , Cell Differentiation , Female , Humans , Pregnancy , T-Lymphocytes, Regulatory/enzymology
8.
Dokl Biochem Biophys ; 474(1): 168-172, 2017 May.
Article in English | MEDLINE | ID: mdl-28726100

ABSTRACT

We investigated the effect of human chorionic gonadotropin, estriol, leptin, ghrelin, and kisspeptin on the microRNA expression in separated NK cells. All of these hormones are able to effectively modulate the expression of microRNAs both stimulating and suppressing the cytotoxic potential of NK cells and thereby indirectly regulate the functions of these lymphocytes.


Subject(s)
Hormones/pharmacology , Killer Cells, Natural/cytology , Killer Cells, Natural/drug effects , MicroRNAs/genetics , Female , Gene Expression Regulation/drug effects , Humans , Pregnancy , Reproduction/drug effects
9.
Dokl Biol Sci ; 472(1): 28-30, 2017 Jan.
Article in English | MEDLINE | ID: mdl-28429258

ABSTRACT

The effects of chorionic gonadotropin, estriol (E3), leptin, ghrelin, and kisspeptin on the intracellular expression of perforin, granzyme A, and granzyme B was studied in separated NK cells. All studied hormones except E3 are could modulate the expression of cytotoxic enzymes in NK cells by suppression of the expression of the most active proapoptotic agents, resulting in increased expression of granzyme A, which is typical of the decidual subpopulation of these lymphocytes.


Subject(s)
Decidua/immunology , Hormones/immunology , Immunity, Cellular/physiology , Killer Cells, Natural/immunology , Pregnancy/immunology , Adult , Female , Granzymes/immunology , Humans , Perforin/immunology
10.
Dokl Biol Sci ; 470(1): 249-252, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27822754

ABSTRACT

Both leptin and ghrelin used separately at the concentrations corresponding to trimesters II-III of pregnancy increase the number of CD56bright NK cells in mononuclear cell suspension; their combination also enhances the L-selectin expression on the surface of these cells in the culture. These hormones do not affect the production of TGF-ß1, IL-17А, or IFN-γ by NK cells, and they inhibit the production of IL-10. Leptin decreses the IL-4 production by NKp46+ cells, but the presence of ghrelin abrogates this effect.


Subject(s)
Cytokines/metabolism , Ghrelin/immunology , Killer Cells, Natural/cytology , Killer Cells, Natural/metabolism , Leptin/immunology , Adult , Cell Proliferation/physiology , Cells, Cultured , Female , Gene Expression Regulation/immunology , Humans , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/immunology
11.
Fiziol Cheloveka ; 42(5): 102-107, 2016 09.
Article in Russian | MEDLINE | ID: mdl-29932555

ABSTRACT

The influence of chorionic gonadotropin (CG) and estriol (E3) at concentrations typical of pregnancy on the expression of phenotypic markers and cytokine production by separated NK cells were studied. It is found that these hormones increase the percentage of CD56brightL-selectin+ NK-cells, but also stimulate the expression of the inhibitory molecule NKG2A in the lymphocytes. In addition, E3 and CG stimulate the production of TGF-B, inhibiting the secretion of all other cytokines by separated NK cells. In general, these hor- mones contribute to the formation of the phenotype and cytokine spectrum characteristic of the regulatory NK3 subpopulation of NK cells during pregnancy.


Subject(s)
Chorionic Gonadotropin , Estriol , Killer Cells, Natural , Chorionic Gonadotropin/physiology , Estriol/physiology , Humans , Killer Cells, Natural/physiology , Phenotype
12.
Bull Exp Biol Med ; 160(1): 72-5, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26597689

ABSTRACT

The role of oligopeptides of chorionic gonadotropin ß-subunit (LQGV, AQGV, and VLPALP) in induction of differentiation into T-regulatory lymphocytes (Treg) and IL-17-producing lymphocytes (Th17) was studied in an in vitro system. Chorionic gonadotropin and oligopeptides promoted CD4(+) cell differentiation into functionally active Treg (FOXP3(+)GITR(+) and FOXP3(+)CTLA-4(+)), while chorionic gonadotropin and AQGV additionally stimulated IL-10 production by these cells. In parallel, chorionic gonadotropin and oligopeptides prevented CD4(+) cell differentiation into Th17 lymphocytes (ROR-gt(+)IL-17A(+)) and suppressed IL-17A secretion. Hence, oligopeptides of chorionic gonadotropin ß-subunit promoted differentiation of CD4(+) cells into Treg and, in parallel, suppress Th17 induction, thus virtually completely reproducing the effects of the hormone, which opens new vista for their use in clinical practice.


Subject(s)
CD4-Positive T-Lymphocytes/drug effects , Chorionic Gonadotropin, beta Subunit, Human/pharmacology , Lymphopoiesis/drug effects , T-Lymphocytes, Regulatory/cytology , Th17 Cells/cytology , Adult , Chorionic Gonadotropin, beta Subunit, Human/chemistry , Drug Evaluation, Preclinical , Female , Humans , Interleukin-10/biosynthesis , Interleukin-17/biosynthesis , Interleukin-1beta/pharmacology , Interleukin-6/pharmacology , Peptide Fragments/pharmacology , T-Lymphocytes, Regulatory/metabolism , Th17 Cells/metabolism
13.
Dokl Biol Sci ; 464: 267-9, 2015.
Article in English | MEDLINE | ID: mdl-26530074

ABSTRACT

The effect of kisspeptin at concentrations typical of pregnancy on the functional activity of isolated cytokine-primed NK cells has been investigated. The hormone has been shown to promote an increase in the proportion of CD56(bright) NK cells, as well as an increase in the L-selectin expression on the cell surface. Assessment of cytokine levels has shown that kisspeptin suppresses the production of IL-4, IL-10, and IFN-γ while stimulating the production of TGF-ß by isolated NK cells. The overall effect of the hormone investigated consisted in the formation of a phenotype and a cytokine spectrum characteristic of the regulatory NK3 subpopulation of NK cells in pregnancy.


Subject(s)
Killer Cells, Natural/drug effects , Kisspeptins/pharmacology , Adult , Cells, Cultured , Female , Humans , Interferon-gamma/genetics , Interferon-gamma/metabolism , Interleukin-10/genetics , Interleukin-10/metabolism , Interleukin-4/genetics , Interleukin-4/metabolism , Killer Cells, Natural/metabolism , L-Selectin/genetics , L-Selectin/metabolism , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolism
16.
Article in Russian | MEDLINE | ID: mdl-25536774

ABSTRACT

AIM: Study the effect of Escherichia coli acellular metabolites of various phases of development on phagocytic activity of neutrophils against the background of pregnancy hormone effect--estriol (E3). MATERIALS AND METHODS: E. coli K12 (wt) metabolites were selected at the end of adaptation and logarithmic growth phases by filtration after cultivation at 37 degrees C in LB broth. Neutrophils of heparinized venous blood of healthy non-pregnant women (follicular phase, n = 8) were incubated for 1 hour with E3 at 2 ng/ml and 20 ng/ml, then 30 minutes with E. coli metabolites, LB medium or Hanks' solution at 37 degrees C. Phagocytic activity evaluation was carried out by inhibition of bioluminescence of E. coli K12 TG1 lux+. RESULTS: Exometabolites of logarithmic growth phase of E. coli culture inhibited neutrophil phagocytosis after 40 - 60 minutes of incubation in contrast to metabolites of adaptation phase compared with LB medium. Neutrophil cultivation after hormone treatment in LB medium that has the ability to stimulate neutrophil phagocytosis compared with Hanks' solution did not alter their phagocytic activity. However inhibiting effect of E3 at 20 ng/ml on neutrophil phagocytosis compared with control was exhibited in Hanks' solution (at 50 - 60 minutes) and after the effect of E. coli adaptation phase metabolites (at 40 - 60 minutes). CONCLUSION: E3 at the level extrapolated from its level at III trimester of pregnancy could facilitate the reduction of antimicrobial potential of neutrophils at the early stages of growth of pathogenic microorganisms.


Subject(s)
Escherichia coli/metabolism , Estriol/biosynthesis , Neutrophils/metabolism , Phagocytosis , Anti-Infective Agents/metabolism , Escherichia coli/pathogenicity , Estriol/metabolism , Female , Humans , Microbiota , Neutrophils/microbiology , Pregnancy
19.
Bull Exp Biol Med ; 156(6): 819-22, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24824706

ABSTRACT

We studied isolated and combined effects of leptin and ghrelin on the formation of IL-producing and T-regulatory cells. Leptin in concentrations comparable with its normal blood concentration during pregnancy (trimester II-III) promotes differentiation of peripheral blood CD4(+) cells to IL-17-producing cells and enhances IL-17A production, but suppresses the formation of T-regulatory cells in vitro. In contrast, ghrelin in a concentration typical of trimester I-II of pregnancy reduces the number of IL-17-producing cells, but stimulated the formation of T-regulatory cells. The effects of leptin and ghrelin in combination typical of trimester I-II of pregnancy stimulated the formation of T-regulatory cells, while in combination typical of trimester II-III did not shift the balance of T-regulatory cells and IL-17-producing cells, but stimulated the formation of IL-17A. We conclude that leptin and ghrelin play an important role in the maintenance of the balance of IL-17-producing and T-regulatory cells during pregnancy.


Subject(s)
CD4-Positive T-Lymphocytes/drug effects , Cell Differentiation/drug effects , Ghrelin/pharmacology , Interleukin-17/metabolism , Leptin/pharmacology , T-Lymphocytes, Regulatory/physiology , Adult , CD4-Positive T-Lymphocytes/metabolism , Female , Flow Cytometry , Fluorescence , Forkhead Transcription Factors/metabolism , Humans , Leukocytes, Mononuclear , Pregnancy , T-Lymphocytes, Regulatory/drug effects
SELECTION OF CITATIONS
SEARCH DETAIL
...