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S Tabibzadeh

Publications and source records attributed to S Tabibzadeh.

51 records · Page 3Linked to original sources
PubMed1992

Cytokine expression in human endometrium throughout the menstrual cycle.

Recent evidence suggests that diverse endometrial functions may be regulated by cytokines. In this report, the presence of protein and mRNA of cytokines were studied in human endometrium throughout the menstrual cycle. The presence of the interleukin-1 (IL-1) alpha, interleukin-1 (IL-1) beta, interleukin receptor antagonist (IRAP), interleukin-6 (IL-6) and transforming growth factor (TGF)-alpha proteins were demonstrated by immunohistochemical staining. The IL-1 alpha and TGF-alpha proteins were strongly expressed and IL-1 beta protein was weakly expressed in all the cells in the stroma as well as epithelial cells. IRAP was markedly expressed in the cells with morphological features of macrophages scattered in the stroma, and the expression of IL-6 protein was predominant in the endometrial epithelium. Diffuse cytoplasmic expression of IL-1 alpha in endometrial epithelium during the proliferative phase contrasted markedly with its enhanced luminal expression during the secretory phase of the menstrual cycle. In addition, the presence of the mRNA of these cytokines in endometrium was established throughout the entire menstrual cycle by reverse transcription-polymerase chain reaction (RT-PCR). Abundant expression of cytokines in human endometrium emphasizes the significant roles that cytokines play in cell-cell interactions and in regulating endometrial functions.

Actins↗
PubMed1992

Tumor necrosis factor-alpha messenger ribonucleic acid and protein in human endometrium.

Although previous studies have shown that the tumor necrosis factor-alpha (TNF) gene is expressed in pregnancy decidua, it has not been determined whether this gene is transcribed or translated in the endometrium prior to implantation. To address this question and to identify cells expressing the TNF gene, samples of normal cycling human endometria were tested for TNF mRNA by in situ hybridization using a biotinylated antisense RNA probe, and the corresponding protein was localized in the same tissues by immunocytochemistry with a monoclonal antibody to TNF. Both TNF message and protein were identified in the endometrium throughout the menstrual cycle, and the same types of cells that contained transcripts also contained protein. As judged by the intensities of the hybridization signals, TNF mRNA increased during the proliferative phases, declined in the early secretory phase, and again rose during mid-to-late secretory phases, suggesting positive associations with levels of female sex hormones that show similar cyclic fluctuations. At the initiation of the cycle, transcripts were primarily localized to glandular epithelial cells whereas by the midproliferative phase, message was also present in stromal cells. Hybridization signals were consistently more intense in functionalis-region than in basalis-region stromal cells, and were frequently stronger in basalis-region glandular epithelia than in functionalis-region glands. These observations document that the TNF gene is expressed in normal cycling endometria, suggest that ovarian hormones may regulate TNF gene transcription, and identify differences in specific endometrial compartments. The findings are also consistent with the postulate that TNF is a local mediator of cellular communications in the human endometrium.

Adult↗
PubMed1991

Ubiquitous expression of TNF-alpha/cachectin immunoreactivity in human endometrium.

Emerging evidence suggests that cytokines play significant roles as intercellular communication signals in human endometrium. In the present report, an immunohistochemical staining method and tumor necrosis factor-alpha (TNF-alpha) specific polyclonal antibody was used to identify potential in vivo sources of this cytokine in human endometrium. During the proliferative and early secretory phases of the menstrual cycle, glandular epithelium was distinctly free of any immunoreactive product. With the emergence of mid- and particularly late-secretory phases, however, some glandular epithelial cells started to express TNF-alpha. In the late secretory phase, glands exhibiting strong staining were adjacent to those that were negative for TNF-alpha or only sparingly contained positively immunostained cells. Remarkably, the glandular epithelium constituted a major source of enhanced expression of TNF-alpha during gestation. In the proliferative phase, virtually all stromal cells strongly expressed TNF-alpha, and in the secretory phase, some variability of staining could be observed among various stromal cells. In gestational endometria, decidual cells and in all endometria, endothelial cells strongly expressed immunoreactivity for TNF-alpha. These data demonstrate that various constituents of endometria are constitutively primed to express TNF-alpha and that this expression is distinctly associated with the changes in endometrium that are compelled by hormonal stimuli.

Adult↗
PubMed1991

Distinct subsets of stromal cells confined to unique microenvironments in human endometrium throughout the menstrual cycle.

Human endometrial stroma exhibits rather uniform morphology throughout the endometrium. However, predecidualization develops characteristically around vessels and subsequently around glands and under surface epithelium, demonstrating existence of regional differences among stromal cells. Immunoreactivity of stromal cells in endometrial tissues from various phases of the menstrual cycle, as elucidated by employing monoclonal antibodies to cytokeratin, vimentin, very late antigen-1 (VLA-1), Ber-EP4, and HLA-DR, revealed presence of phenotypically distinct subsets of stromal cells confined to unique microenvironments throughout the menstrual cycle. All stromal cells strongly expressed vimentin and weakly expressed cytokeratin. However, Ber-EP4 positive stromal cells were distinctly confined around glands and to the subluminal regions of the surface epithelium. The intervening stromal cells were Ber-EP4 negative. The HLA-DR positive stromal cells were characteristically present in three different locations: around glands and under surface epithelium, around blood vessels and around HLA-DR positive lymphoid cells. From all antigens studied, only expression of VLA-1 in the stromal cells showed a characteristic change throughout the menstrual cycle. Stromal cells in the proliferative and early secretory phases were VLA-1 negative. However, VLA-1 characteristically developed initially in the HLA-DR positive cells around vessels and then in HLA-DR/Ber-EP4 positive cells around glands and under surface epithelium. Eventually, all stromal cells in the upper functionalis expressed VLA-1 in the late secretory phase of the menstrual cycle. These data underscore a heterogeneity in stromal cells not exemplified by their morphology. Also, they provide a basis for understanding the differences that the stroma exhibits in morphologic and functional differentiation throughout the menstrual cycle.

Adult↗
PubMed1991

Cytokine regulation of human endometrial function.

Human endometrium undergoes sequences of proliferation, and secretion followed by menstruation in a predictable fashion. The importance of systemic factors, steroid hormones, in driving endometrium through these phases is well known. However, it is becoming increasingly apparent that a group of factors collectively called cytokines may also serve a key role as local modulators of endometrial function. Expression of the receptors for cytokines, production of cytokines and the ability to demonstrate modulation of a host of functions of both endometrial epithelium and stroma indicate that human endometrium is uniquely poised to respond to cytokines.

Cytokines↗
PubMed1991

Induction of HLA-DR expression in endometrial epithelial cells by endometrial T-cells: potential regulatory role of endometrial T-cells in vivo.

Endometrial epithelial cells express HLA-DR molecules of the major histocompatibility complex in vivo adjacent to aggregates of T-cells in the endometrial stroma. To test whether HLA-DR expression on endometrial epithelium is mediated by T-cells, endometrial T-cells were isolated from human endometrium by the sheep red blood cell rosetting technique. In contrast to the resting T-cells from peripheral blood and similar to the peripheral blood T-cells activated with Concanavalin-A, endometrial T-cells formed colonies in vitro. Direct addition of the endometrial T-cells to epithelial cell cultures derived from autologous glands induced both morphological changes as well as HLA-DR molecules in the epithelial cells. The intensity of the immunostained HLA-DR molecules in the epithelial cells as well as the percentages of the HLA-DR-positive epithelial cells correlated with the number of T-cells added to the epithelial cell cultures. T-Cells were bound to the HLA-DR-positive epithelial cells as single cells or aggregates, and they were not found bound to the HLA-DR-negative epithelial cells. The supernatant of the endometrial T-cells induced expression of HLA-DR molecules and morphological changes in cultures of HLA-DR-negative epithelial cells. This expression could be inhibited by a neutralizing antiserum to interferon-gamma. These findings are consistent with the hypothesis that endometrial T-cells are activated and suggest that the expression of HLA-DR molecules in glandular epithelium in vivo is mediated by the interferon-gamma secreted by the endometrial T-cells.

Adult↗
PubMed1991

Expression of colony-stimulating factor-1 (CSF-1) messenger RNA in human endometrial glands during the menstrual cycle: molecular cloning of a novel transcript that predicts a cell surface form of CSF-1.

Colony-stimulating factor-1 (CSF-1) has been primarily characterized as a hematopoietic growth factor required for the proliferation and differentiation of monocytic cells. Recent immunohistological observations have shown that this growth factor is also synthesized by the glandular epithelial cells of the pregnant human endometrium and by first trimester human trophoblasts. In the present study endometrial glands were purified from nonpregnant human endometria collected through the menstrual cycle and examined for CSF-1 mRNA expression. The two major mRNAs (4.0 and 3.0 kilobases in length) detected in midproliferative and midsecretory phases differed in the size of the exon 6 and coded, respectively, for a secreted and a cell surface form of CSF-1. The 3.0-kilobase transcript represented a novel CSF-1 mRNA species that was molecularly cloned and sequenced. These data raise the possibility that CSF-1 may be involved in both distant and cell to cell regulatory pathways of cell proliferation and differentiation in the human endometrium.

Base Sequence↗
PubMed1990

Human endometrial epithelial cell lines for studying steroid and cytokine actions.

Recent studies suggest that the proliferation and expression of HLA-DR molecules in endometrial epithelium may be regulated by systemic steroids and local cytokines. To test the interacting influences of cytokines and steroids on the expression of HLA-DR and proliferation of epithelial cells, an endometrial cell model is required that is sensitive to both signals. In this study, we characterize cells of carcinoma cell lines of endometrial lineage for their responsiveness to cytokines and steroids. Independently developed for its response to steroid hormones from a well-differentiated adenocarcinoma of human endometrium, EnCa101AE cell line is further cloned for the expression of progesterone receptor. Immunohistochemical localization using monoclonal antibodies demonstrates that both EnCa101AE cell line and cloned ECC1 cells are purely epithelial, as evidenced by the expression of cytokeratin and epithelial membrane antigen, express estrogen receptors, and concomitantly exhibit IFN-gamma receptor. Experiments using radioiodinated IL-1 reveal that these cell lines also possess high affinity receptors for IL-1. As indicated by the induction of HLA-DR molecules, and alterations in morphologic characteristics, these cell lines are sensitive to both IFN-gamma and IL-1 action. The class II molecules (HLA-DR, HLA-DP, and HLA-DQ) are differentially induced by IFN-gamma treatment in carcinoma cell lines, with HLA-DR being the prevailing induced molecule. IFN-gamma inhibits and estradiol-17 beta promotes growth of ECC1 cells in a dose- and time-dependent manner. These findings indicate that the interacting effect(s) of the cytokines and steroid hormones on endometrial epithelium may be studied in these unique steroid- and cytokine-sensitive epithelial cell lines.

Adenocarcinoma↗
PubMed1990

Proliferative activity of lymphoid cells in human endometrium throughout the menstrual cycle.

Human endometrium harbors a major population of lymphoid cells. The proliferation of these cells is assessed by the in situ labeling of endometrial sections for Ki67 (a proliferation marker) as well as in vitro incorporation of bromodeoxyuridine (BrdU; a thymidine analog) into S-phase cells in vibratome sections of endometria. Using the avidin-biotinperoxidase complex method, sections of endometria and vibratome sections of endometria are labeled for Ki67 and BrdU, respectively. Subsequently, they are immunostained for CD45 (a lymphoid cell marker), CD3 (a T cell marker), and CD11c (a macrophage marker) molecules. Lymphoid cells scattered or aggregated in the endometrial stroma as well as intraglandular lymphoid cells exhibit Ki67 positivity throughout the menstrual cycle. The proliferative activity of the lymphoid cells, including the CD45, CD3, and CD11c positive cells scattered in the stroma, is markedly increased in the secretory phase. Similar, however less conspicuous, increased Ki67 labeling is observed in the lymphoid cells within lymphoid aggregates. The increased proliferative activity of the lymphoid cells in the secretory phase is confirmed by BrdU labeling in the vibratome sections. In the proliferative phase the non-CD45-positive cells in the endometrial stroma exhibit low proliferative activity, and in the secretory phase, Ki67 labeling in the endometrial stroma is primarily confined to the CD45-positive cells. The findings suggest that in situ proliferation is one mechanism by which the endometrial lymphoid cell pool within endometrium is restored after each menstrual shedding.

Affinity Labels↗
PubMed1990

Interleukin-1 (IL-1) regulation of human endometrial function: presence of IL-1 receptor correlates with IL-1-stimulated prostaglandin E2 production.

Previous studies suggest that prostaglandin E2 (PGE2) is important in normal endometrial function and that it may be involved in certain uterine dysfunctions. In this study, the ability of the purified E. coli-derived recombinant interleukin-1 alpha (rIL-1 alpha) to regulate the production of PGE2 by the endometrial epithelium is investigated. PGE2 levels determined by the RIA consistently increase upon incubation of cultured glandular epithelial cells with rIL-1 alpha. A significant increase is obtained with 17 and 170 ng/L rIL-1 alpha. A maximal effect is obtained within 24 h of incubation with rIL-1 alpha. In the seven endometria evaluated, rIL-1 alpha increases PGE2 synthesis in all cases, but the maximal increase relative to the basal levels varies between 2- to 10-fold for a given preparation. Vibratome sections retaining the integrity of the endometrial tissue also show an increased PGE2 synthesis in response to rIL-1 alpha. rIL-1 alpha-stimulated PGE2 production is blocked by the addition of a neutralizing antibody to rIL-1 alpha. In addition, indomethacin, a cyclooxygenase inhibitor, suppresses both rIL-1 alpha-induced and basal PGE2 synthesis. Experiments using radioiodinated rIL-1 alpha reveal that the membranes prepared from human endometrial epithelium possess high affinity receptors for IL-1, suggesting that IL-1 regulates PGE2 synthesis by binding to this receptor site. The expression of IL-1 receptors and the ability to modulate PGE2 production by IL-1 in endometrial epithelium suggest that IL-1 may play a significant role in human uterine function via modulation of PGE2 production.

Adult↗
PubMed1990

Evidence of T-cell activation and potential cytokine action in human endometrium.

Antigenic epitopes have been described whose expression characterizes early or late stages of activation of T-cells. In this study the expression of early activation antigen, interleukin-2 receptor was compared with the expression of late activation antigens, HLA-DR, HLA-DP, and HLA-DQ molecules of the major histocompatibility complex II, and very late activation antigen, VLA-1 of the integrin superfamily of molecules in 43 human endometria. These molecules were localized by their reactivity with monoclonal antibodies in an avidinbiotin-complex procedure. Interleukin-2 receptor was not expressed in human endometria; however, endometrial T-cells within lymphoid aggregates, some scattered in endometrial stroma and a few within epithelium, expressed HLA-DR, HLA-DP, HLA-DQ, and VLA-1. In addition, expression of the receptor of interferon-gamma, a product of activated T-cells, was observed on endometrial epithelium. Evidence for activation of T-cells and expression of interferon-gamma receptor in human endometrial epithelium suggests that endometrium may be an active site for cytokine action.

Adult↗
PubMed1990

Immunoreactivity of human endometrium: correlation with endometrial dating.

Human leukocyte antigen (HLA)-DR molecules of the major histocompatibility complex II, very late antigen-1 of the integrin superfamily of molecules, B72.3 (a tumor-associated glycoprotein), Ki67 (a marker of proliferation), and epithelial membrane antigen (EMA, a high molecular weight glycoprotein) were found to have distinctive localization within endometrium throughout the menstrual cycle. These molecules were localized by avidin-biotin-complex procedure in 26 endometria dated to midproliferative, late proliferative, early secretory, midsecretory, and late secretory phases of the menstrual cycle. Proliferative phase of the menstrual cycle was characterized by expression of Ki67 and HLA-DR and absence of very late antigen-1, B72.3, and EMA in endometrial glands. Secretory phase of the menstrual cycle was marked by the appearance and persistence of very late antigen-1, B72.3, and EMA in glandular epithelium. In addition, the solid compactum of the late secretory phase was marked by the development of very late antigen-1 in the predecidual cells. These findings demonstrate that the immunoreactivity of human endometrium is under the same constraints that compel the endometrium to undergo morphological changes.

Adult↗
PubMedDate not supplied

Molecular control of the implantation window.

Human endometrium is the end organ of the hypothalamic-pituitary-ovarian axis. Therefore, endometrium is susceptible to changes in the cases of infertility that originate from disturbances in the normal functioning of this axis. In addition, some cases of unexplained infertility may be due to altered endometrial function. This disturbed endometrial function may originate from lesions in the molecular repertoire that are crucial to implantation. Human endometrium becomes receptive to implantation by the blastocyst within a defined period during the menstrual cycle. The duration of this so-called 'endometrial receptivity' or 'implantation' period seems to span from few days after ovulation to several days prior to menstruation. Successful implantation results from a co-ordinated series of events that would allow establishment of a timely dialogue between a receptive endometrium and an intrusive blastocyst. The members of the molecular repertoire that make endometrium receptive to implantation are gradually being recognized. Among these are the cytokines, integrins, heat shock proteins, tastin and trophinin. In addition, the expression of a second set of genes including tumour necrosis factor alpha (TNF-alpha) and ebaf, may be the appropriate signal for the closure of the 'implantation window', for making the endometrium refractory to implantation and for preparing it for the menstrual shedding.

Animals↗