ABSTRACT
We studied changes in angiogenesis during contact interaction of natural killer cells and endothelial cells in the presence of secretory products of trophoblast cells activated by various cytokines. Activated trophoblast regulates angiogenesis by producing soluble factors that affect endothelial cells either directly or indirectly through activation of proangiogenic activity of natural killer cells. A stimulating effect of the trophoblast supernatants activated by IL-1ß and an inhibitory effect of trophoblast supernatants activated by IL-6 and TGFß for the formation of tube-like structures by endothelial cells were revealed. During contact culturing, natural killer cells increased the length of tube-like structures formed by endothelial cells. The trophoblast activated by IL-1ß affects angiogenesis both directly through the production of proangiogenic factors and indirectly through activation of the proangiogenic potential of natural killer cells. Trophoblast activated by IFNγ affects angiogenesis only by stimulating the proangiogenic potential of natural killer cells. Under conditions of contact interaction of natural killer cells and endothelial cells, soluble factors of trophoblast activated by IL-6 or TGFß attenuated the angiogenesis-stimulating effect of natural killer cells.
Subject(s)
Endothelial Cells/cytology , Endothelial Cells/metabolism , Killer Cells, Natural/cytology , Killer Cells, Natural/metabolism , Trophoblasts/cytology , Trophoblasts/metabolism , Cell Communication/physiology , Cell Line , Cell Line, Tumor , Female , Humans , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Neovascularization, Pathologic/pathology , Transforming Growth Factor beta/metabolismABSTRACT
Despite ample data on cytokine secretion in the uteroplacental interface, the influence of microenvironment cells, in particular, trophoblast cells on angiogenesis and the role of cytokines in this process remain poorly studied. We studied the influence of cytokines on the formation of tube-like structures by endothelial cells in the presence of trophoblast cells and showed that trophoblast cells suppressed the angiogenic potential of endothelial cells. Antiangiogenic cytokines IFN-γ, IL-10, TNF-α, and TGFß via modulation of trophoblast cells stimulated the formation of tube-like structures by endothelial cells. In the co-culture of endothelial and trophoblast cells, the effects of cytokines changed and they gained additional regulatory functions.
Subject(s)
Cytokines/pharmacology , Endothelial Cells/cytology , Endothelial Cells/drug effects , Trophoblasts/cytology , Trophoblasts/drug effects , Cell Line , Female , Humans , Interleukin-10/pharmacology , Interleukin-6/pharmacology , Interleukin-8/pharmacology , Placenta/cytology , Pregnancy , Tumor Necrosis Factor-alpha/pharmacologyABSTRACT
We studied the effects of secretory products of the placenta obtained from women with normal pregnancy and preeclampsia on the expression of surface markers by THP-1 cells cultured on a 3D Matrigel scaffold. Secretory products of third trimester placentas obtained from women with normal pregnancy reduced the relative number of THP-1 cells expressing CD54 and CD14 molecules and expression of CD14 and CD95 molecules by THP-1 cells in comparison with the effect of secretory products first trimester placentas. In parallel, the intensity of CD49d expression by THP-1 cells increased in the presence of secretory products of third trimester placentas in comparison with the first trimester. No differences in the expression of the studied molecules by THP-1 cells under the effect of placentas from women with physiological pregnancy and patients with preeclampsia were found.
Subject(s)
Macrophages/metabolism , Placenta/metabolism , Pre-Eclampsia/metabolism , Antigens, CD/metabolism , Cell Culture Techniques , Cell Line , Female , Humans , Phenotype , Pregnancy , Pregnancy Trimester, First , Pregnancy Trimester, ThirdABSTRACT
TNFα inhibited proliferation and did not inhibit migration JEG-3 trophoblast cells, IL-1ß stimulated both cell proliferation and migration, IL-6 and IL-8 stimulated only cell migration, IFNγ has either stimulating or inhibitory effect on proliferation of trophoblast cells depending on its concentration. Cytokines IL-10 and IL-4 stimulated only migration of trophoblast cells. VEGF, PlGF, and TGFß stimulated both proliferation and migration, and bFGF only migration of trophoblast cells.
Subject(s)
Cytokines/physiology , Trophoblasts/physiology , Cell Line , Cell Movement , Cell Proliferation , HumansABSTRACT
The interaction of endothelial cells with cells of the microenvironment, including monocytes/ macrophages, and extracellular matrix during angiogenesis is controlled by cytokines. The stimulating effect bFGF, IL-8, and VEGF on the formation of capillary-like structures by endothelial cells was demonstrated in both monoculture and in co-culture with THP-1 cells; in the latter case, the effects of bFGF and VEGF were more pronounced. IL-8 reduced branching of vascular tubes in co-culture in comparison with monoculture of endothelial cells. Placental growth factor PlGF had no effect of tube formation by endothelial cells in monoculture, but in co-culture with THP-1 cells this cytokine in high concentrations exhibited proangiogenic activity. TGFb inhibited the formation of vascular tubes by endothelial cells and its antiangiogenic potential was more pronounced in co-culture with THP-1 cells.
Subject(s)
Capillaries/growth & development , Endothelial Cells/cytology , Endothelium, Vascular/growth & development , Monocytes/cytology , Neovascularization, Physiologic/physiology , Cell Differentiation , Cell Line , Coculture Techniques , Fibroblast Growth Factors/pharmacology , Humans , Interleukin-8/pharmacology , Placenta Growth Factor , Pregnancy Proteins/pharmacology , Vascular Endothelial Growth Factor A/pharmacologyABSTRACT
We studied the influence of factors secreted by the placenta in physiological and preeclampsia-complicated pregnancy on migration activity of endothelial EA.Hy926 cells. It was found that migration of endothelial cells was more intensive in the presence of secretory factors from trimester I placentas in comparison with trimester III placentas and was lower in the presence of placental factors in preeclampsia in comparison with physiological pregnancy.
Subject(s)
Cell Movement , Endothelial Cells/physiology , Placenta/metabolism , Pre-Eclampsia/metabolism , Adolescent , Adult , Cell Line , Culture Media , Female , Humans , Pregnancy , Tissue Culture Techniques , Tissue Extracts/physiology , Young AdultABSTRACT
The formation of vascular tubules by EA.Hy926 endothelial cells was studied in the presence of placental secretory products from women with normal gestation at early and late periods and with gestosis. The factors secreted by placental tissues at the early stages of placental development stimulated the branching angiogenesis, while the products of the end of pregnancy stimulated nonbranching angiogenesis. In gestosis the placental tissue secreted products stimulating even more intense nonbranching angiogenesis, which manifested by a lesser number of branchings of vascular tubes formed by EA.Hy926 endothelial cells.
Subject(s)
Blood Vessels/embryology , Neovascularization, Physiologic , Placenta/metabolism , Pre-Eclampsia/metabolism , Blood Vessels/growth & development , Cell Line , Endothelial Cells/physiology , Endothelium, Vascular , Female , Humans , Placentation , Pre-Eclampsia/blood , PregnancyABSTRACT
We studied the effects of soluble products of the placental tissue from women with normal pregnancy and gestosis on the cytokine secretion by endothelial EA.Hy926 cells. The secretory products of the placental tissue induced the production of angiogenin, bFGF, IL-8, MCP-1, and RANTES by endothelial cells. The secretion of bFGF by EA.Hy926 cells increased, while IL-8 secretion decreased under the effects of factors produced by the placental tissue in gestosis but not in normal pregnancy. This could be aimed at reduction of inflammation intensity in the placental tissue and maintenance of endothelial and trophoblast cells viability.
Subject(s)
Cytokines/metabolism , Endothelial Cells/metabolism , Placenta/cytology , Placenta/metabolism , Pre-Eclampsia/metabolism , Cell Line , Chemokine CCL2/metabolism , Chemokine CCL5/metabolism , Female , Fibroblast Growth Factor 2/metabolism , Humans , Interleukin-8/metabolism , Pregnancy , Ribonuclease, Pancreatic/metabolism , Trophoblasts/metabolismABSTRACT
In the present review modern data about change of morfo-functional properties of a trophoblast during pregnancy, and also about influence of the cytokines produced by cells of a microenvironment, including leucocytes of mother, on a functional state of trophoblast is cited. Features of interaction between trophoblast and immune cells of mother are described within physiological pregnancy and within pregnancy complicated by preeclampsia.
Subject(s)
Immunity, Cellular , Maternal-Fetal Exchange/immunology , Mothers , T-Lymphocyte Subsets/immunology , Trophoblasts/immunology , Antigen Presentation , Female , Humans , PregnancyABSTRACT
The localization of apoptosis and expression of proapoptotic and antiapoptotic factors by the placental tissue were compared during normal pregnancy and gestosis-complicated pregnancy. The degree of apoptosis did not differ in the third trimester of normal pregnancy and gestosis-complicated pregnancy. Increased expression of Fas, caspase-8, and caspase-3 in placental tissue during normal pregnancy was shown to contribute to the suppression of angiogenesis and growth of placental tissue. No differences were found in the expression of FasL (CD95L), caspase-2, caspase-9, and Mcl-1 by placental cells during normal pregnancy and gestosis-complicated pregnancy. Increased expression of TRAIL by trophoblast cells is a protective mechanism from apoptotic signals of maternal cytotoxic lymphocytes and NK cells during gestosis.
Subject(s)
Apoptosis/physiology , Placenta , Pre-Eclampsia , Biomarkers/metabolism , Caspase 2/metabolism , Caspase 9/metabolism , Fas Ligand Protein/metabolism , Female , Gestational Age , Humans , Myeloid Cell Leukemia Sequence 1 Protein , Placenta/pathology , Placenta/physiology , Pre-Eclampsia/pathology , Pre-Eclampsia/physiopathology , Pregnancy , Proto-Oncogene Proteins c-bcl-2/metabolismABSTRACT
Vascular endothelial growth factors VEGF-A and VEGF-C are the main angiogenic factors that control growth of new blood and lymphatic vessels in the organism, and they also possess several immunoregulatory activities. Expression of VEGF-A and VEGF-C mRNA as well as mRNA for VEGF receptors in lymphocytes and macrophages of naive mice was investigated. Using reverse transcription and subsequent polymerase chain reaction, we found that peritoneal macrophages, thymocytes, and lymph node cells constitutively expressed VEGF-A and VEGF-C mRNA. In addition, macrophages were positive for VEGFR-1, VEGFR-2, VEGFR-3, NRP-1, and NRP-2 mRNA, whereas thymocytes and lymph node cells expressed mRNA of the same receptors except VEGFR-1. These data expand our knowledge concerning gene distribution of VEGF receptors in the organism, in particular, among the cells of the immune system. This suggests that, along with their major angiogenic properties, VEGF family members additionally might also perform important mediatory functions within the immune system.
Subject(s)
Lymphocytes/metabolism , Macrophages, Peritoneal/metabolism , Receptors, Vascular Endothelial Growth Factor/genetics , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor C/genetics , Animals , Base Sequence , Cell Line, Tumor , DNA Primers/genetics , Gene Expression , Male , Mice , Mice, Inbred C3H , Neuropilin-1/genetics , Neuropilin-2/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , T-Lymphocytes/metabolism , Vascular Endothelial Growth Factor Receptor-1/genetics , Vascular Endothelial Growth Factor Receptor-2/genetics , Vascular Endothelial Growth Factor Receptor-3/geneticsABSTRACT
The genetic model of diabetes mellitus was studied on mutant C57Bl/KsLepr(db/+) mice. These mice were characterized by high concentrations of glucose and glycosylated hemoglobin in the blood, polyuria, polyphagia, polydipsia, progressive obesity, biphasic morphological changes in insular islets of the pancreas (hyperplasia and atrophy), fatty degeneration of the liver, and hypoplasia of the spleen tissue and lymph nodes. Our results indicate that C57Bl/KsLepr(db/+) mice serve as an adequate model of type 2 diabetes mellitus. This model is suitable for testing of therapeutic methods for type 2 diabetes mellitus.
