scholarly journals Role of Prolactin and Growth Hormone on Thymus Physiology

1998 ◽  
Vol 6 (3-4) ◽  
pp. 317-323 ◽  
Author(s):  
Valéria De Mello-Coelho ◽  
Wilson Savino ◽  
Marie-Catherine Postel-Vinay ◽  
Mireille Dardenne
Keyword(s):  
Growth Hormone ◽  
Epithelial Cells ◽  
Cell Types ◽  
Pituitary Hormones ◽  
Thymic Epithelial Cells ◽  
Double Positive ◽  
Gh Treatment ◽  
Thymic Hormone

Intrathymic T-cell differentiation is under the control of the thymic microenvironment, which acts on maturing thymocytes via membrane as well as soluble products. Increasing data show that this process can be modulated by classical hormones, as exemplified herein by prolactin (PRL) and growth hormone (GH), largely secreted by the pituitary gland.Both PRL and GH stimulate the secretion of thymulin, a thymic hormone produced by thymic epithelial cells. Conversely, low levels of circulating thymulin parallel hypopituitary states. Interestingly, the enhancing effects of GH on thymulin seem to be mediated by insulinlike growth factor (IGF-1) since they can be abrogated with anti-IGF-1 or anti-IGF-l-receptor antibodies. The influence of PRL and GH on the thymic epithelium is pleiotropic: PRL enhancesin vivothe expression of high-molecular-weight cytokeratins and stimulatesin vitroTEC proliferation, an effect that is shared by GH and IGF-1.Differentiating T cells are also targets for the intrathymic action of PRL and GH.In vivoinoculation of a rat pituitary cell line into old rats results in restoration of the thymus, including differentiation of CD4-CD8-thymocytes into CD4+CD8+cells. Furthermore, PRL may regulate the maintenance of thymocyte viability during the double-positive stage of thymocyte differentiation.Injections of GH into aging mice increase total thymocyte numbers and the percentage of CD3-bearing cells, as well as the Concanavalin-A mitogenic response and IL-6 production by thymocytes. Interestingly, similar findings are observed in animals treated with IGF-1. Lastly, the thymic hypoplasia observed in dwarf mice can be reversed with GH treatment.In keeping with the data summarized earlier is the detection of receptors for PRL and GH on both thymocytes and thymic epithelial cells. Importantly, recent studies indicate that both cell types can produce PRL and GH intrathymically. Similarly, production of IGF-1 and expression of a corresponding receptor has also been demonstrated.In conclusion, these data strongly indicate that the thymus is physiologically under control of pituitary hormones PRL and GH. In addition to the classical endocrine pathway, paracrine and autocrine circuits are probably implicated in such control.

scholarly journals Production of anti-thymulin (FTS) monoclonal antibodies by immunization against human thymic epithelial cells.

1984 ◽  
Vol 32 (4) ◽  
pp. 432-438 ◽  
Author(s):  
S Berrih ◽  
W Savino ◽  
M Azoulay ◽  
M Dardenne ◽  
J F Bach
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Epithelial Cells ◽  
Thymic Epithelial Cells ◽  
Mouse Serum ◽  
Thymic Hormone ◽  
Double Labeling ◽  
Natural Hormone

A monoclonal antibody specific for thymulin (FTS), a thymic hormone initially isolated from serum, was obtained by cell fusion using spleen cells from BALB/c mice immunized with cultured human thymic epithelial cells. Hybridomas were selected according to their capacity to produce antibodies binding specifically to thymic epithelial cells in culture (as assessed by indirect immunofluorescence) and their ability to absorb in vitro the biological activity of synthetic and natural hormone preparations and to induce in vivo the disappearance of endogenous circulating thymulin. In this way monoclonal antibodies were obtained that recognized a subpopulation of nonlymphoid cells on frozen sections of mouse and human thymuses. The epithelial nature of these cells was assessed using an antikeratin antiserum. The binding of the antibodies to thymic cells was completely abolished by its absorption with the synthetic hormone or normal (but not of thymectomized) mouse serum. The thymic specificity of the antibody was further confirmed by the complete absence of binding to sections of all the various lymphoid and epithelial organs examined (from both humans and mice). Double labeling experiments using the monoclonal antibody described above and a monoclonal antibody prepared by immunization with the synthetic peptide showed that the two antibodies bound to the same cell. These results provide further evidence for the exclusive presence of the thymic hormone thymulin in thymic epithelial cells.

scholarly journals Upregulation of the Adhesin Gene EPA1 Mediated by PDR1 in Candida glabrata Leads to Enhanced Host Colonization

mSphere ◽  
2016 ◽  
Vol 1 (2) ◽  
Author(s):  
Luis A. Vale-Silva ◽  
Beat Moeckli ◽  
Riccardo Torelli ◽  
Brunella Posteraro ◽  
Maurizio Sanguinetti ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Epithelial Cells ◽  
Candida Glabrata ◽  
Resistance Mechanism ◽  
Cell Types ◽  
Host Cells ◽  
Regulation Mechanism ◽  
Content Type

ABSTRACT Candida glabrata is an important fungal pathogen in human diseases and is also rapidly acquiring drug resistance. Drug resistance can be mediated by the transcriptional activator PDR1, and this results in the upregulation of multidrug transporters. Intriguingly, this resistance mechanism is associated in C. glabrata with increased virulence in animal models and also with increased adherence to specific host cell types. The C. glabrata adhesin gene EPA1 is a major contributor of virulence and adherence to host cells. Here, we show that EPA1 expression is controlled by PDR1 independently of subtelomeric silencing, a known EPA1 regulation mechanism. Thus, a relationship exists between PDR1, EPA1 expression, and adherence to host cells, which is critical for efficient virulence. Our results demonstrate that acquisition of drug resistance is beneficial for C. glabrata in fungus-host relationships. These findings further highlight the challenges of the therapeutic management of C. glabrata infections in human patients. Candida glabrata is the second most common Candida species causing disseminated infection, after C. albicans. C. glabrata is intrinsically less susceptible to the widely used azole antifungal drugs and quickly develops secondary resistance. Resistance typically relies on drug efflux with transporters regulated by the transcription factor Pdr1. Gain-of-function (GOF) mutations in PDR1 lead to a hyperactive state and thus efflux transporter upregulation. Our laboratory has characterized a collection of C. glabrata clinical isolates in which azole resistance was found to correlate with increased virulence in vivo. Contributing phenotypes were the evasion of adhesion and phagocytosis by macrophages and an increased adhesion to epithelial cells. These phenotypes were found to be dependent on PDR1 GOF mutation and/or C. glabrata strain background. In the search for the molecular effectors, we found that PDR1 hyperactivity leads to overexpression of specific cell wall adhesins of C. glabrata. Further study revealed that EPA1 regulation, in particular, explained the increase in adherence to epithelial cells. Deleting EPA1 eliminates the increase in adherence in an in vitro model of interaction with epithelial cells. In a murine model of urinary tract infection, PDR1 hyperactivity conferred increased ability to colonize the bladder and kidneys in an EPA1-dependent way. In conclusion, this study establishes a relationship between PDR1 and the regulation of cell wall adhesins, an important virulence attribute of C. glabrata. Furthermore, our data show that PDR1 hyperactivity mediates increased adherence to host epithelial tissues both in vitro and in vivo through upregulation of the adhesin gene EPA1. IMPORTANCE Candida glabrata is an important fungal pathogen in human diseases and is also rapidly acquiring drug resistance. Drug resistance can be mediated by the transcriptional activator PDR1, and this results in the upregulation of multidrug transporters. Intriguingly, this resistance mechanism is associated in C. glabrata with increased virulence in animal models and also with increased adherence to specific host cell types. The C. glabrata adhesin gene EPA1 is a major contributor of virulence and adherence to host cells. Here, we show that EPA1 expression is controlled by PDR1 independently of subtelomeric silencing, a known EPA1 regulation mechanism. Thus, a relationship exists between PDR1, EPA1 expression, and adherence to host cells, which is critical for efficient virulence. Our results demonstrate that acquisition of drug resistance is beneficial for C. glabrata in fungus-host relationships. These findings further highlight the challenges of the therapeutic management of C. glabrata infections in human patients.

scholarly journals Proliferative arrest and rapid turnover of thymic epithelial cells expressing Aire

2007 ◽  
Vol 204 (11) ◽  
pp. 2521-2528 ◽  
Author(s):  
Daniel Gray ◽  
Jakub Abramson ◽  
Christophe Benoist ◽  
Diane Mathis
Keyword(s):  
Epithelial Cells ◽  
Flow Cytometric Analysis ◽  
Tolerance Induction ◽  
Brdu Incorporation ◽  
Thymic Epithelial Cells ◽  
High Turnover ◽  
Central Tolerance ◽  
Cross Presentation

Expression of autoimmune regulator (Aire) by thymic medullary epithelial cells (MECs) is critical for central tolerance of self. To explore the mechanism by which such a rare cell population imposes tolerance on the large repertoire of differentiating thymocytes, we examined the proliferation and turnover of Aire+ and Aire− MEC subsets through flow cytometric analysis of 5-bromo-2′deoxyuridine (BrdU) incorporation. The Aire+ MEC subset was almost entirely postmitotic and derived from cycling Aire− precursors. Experiments using reaggregate thymic organ cultures revealed the presence of such precursors among Aire− MECs expressing low levels of major histocompatibility complex class II and CD80. The kinetics of BrdU decay showed the Aire+ population to have a high turnover. Aire did not have a direct impact on the division of MECs in vitro or in vivo but, rather, induced their apoptosis. We argue that these properties strongly favor a “terminal differentiation” model for Aire function in MECs, placing strict temporal limits on the operation of any individual Aire+ MEC in central tolerance induction. We further speculate that the speedy apoptosis of Aire-expressing MECs may be a mechanism to promote cross-presentation of the array of peripheral-tissue antigens they produce.

scholarly journals Effects of Psa and F1 on the Adhesive and Invasive Interactions of Yersinia pestis with Human Respiratory Tract Epithelial Cells

2006 ◽  
Vol 74 (10) ◽  
pp. 5636-5644 ◽  
Author(s):  
Fengzhi Liu ◽  
Huaiqing Chen ◽  
Estela M. Galván ◽  
Melissa A. Lasaro ◽  
Dieter M. Schifferli
Keyword(s):  
Epithelial Cells ◽  
Respiratory Tract ◽  
Yersinia Pestis ◽  
Bacterial Adhesion ◽  
Wild Type Strain ◽  
Cell Types ◽  
Human Respiratory Tract ◽  
Bacterial Uptake

ABSTRACT Yersinia pestis, the causative agent of plague, expresses the Psa fimbriae (pH 6 antigen) in vitro and in vivo. To evaluate the potential virulence properties of Psa for pneumonic plague, an Escherichia coli strain expressing Psa was engineered and shown to adhere to three types of human respiratory tract epithelial cells. Psa binding specificity was confirmed with Psa-coated polystyrene beads and by inhibition assays. Individual Y. pestis cells were found to be able to express the capsular antigen fraction 1 (F1) concomitantly with Psa on their surface when analyzed by flow cytometry. To better evaluate the separate effects of F1 and Psa on the adhesive and invasive properties of Y. pestis, isogenic Δcaf (F1 genes), Δpsa, and Δcaf Δpsa mutants were constructed and studied with the three respiratory tract epithelial cells. The Δpsa mutant bound significantly less to all three epithelial cells compared to the parental wild-type strain and the Δcaf and Δcaf Δpsa mutants, indicating that Psa acts as an adhesin for respiratory tract epithelial cells. An antiadhesive effect of F1 was clearly detectable only in the absence of Psa, underlining the dominance of the Psa+ phenotype. Both F1 and Psa inhibited the intracellular uptake of Y. pestis. Thus, F1 inhibits bacterial uptake by inhibiting bacterial adhesion to epithelial cells, whereas Psa seems to block bacterial uptake by interacting with a host receptor that doesn't direct internalization. The Δcaf Δpsa double mutant bound and invaded all three epithelial cell types well, revealing the presence of an undefined adhesin(s) and invasin(s).

scholarly journals Murine clusterin: molecular cloning and mRNA localization of a gene associated with epithelial differentiation processes during embryogenesis

1993 ◽  
Vol 122 (5) ◽  
pp. 1119-1130 ◽  
Author(s):  
LE French ◽  
A Chonn ◽  
D Ducrest ◽  
B Baumann ◽  
D Belin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Cell Types ◽  
Branching Morphogenesis ◽  
Structural Features ◽  
Heparin Binding ◽  
Binding Domains ◽  
Cell Layers

Clusterin is a broadly distributed glycoprotein constitutively expressed by various tissues and cell types, that has been shown to be involved in cell-cell adhesion and expressed during cellular differentiation in vitro. To assess the suggested participation of clusterin in these processes in vivo, we have cloned the cDNA encoding murine clusterin and studied the cellular distribution of clusterin mRNA during murine embryogenesis. Sequence analysis of the cDNA encoding murine clusterin revealed 92 and 75% sequence identity with the rat and human cDNAs, respectively, and conservation of the predicted structural features which include alpha-helical regions and heparin-binding domains. From 12.5 d of development onwards, the clusterin gene is widely expressed in developing epithelia, and selectively localized within the differentiating cell layers of tissues such as the developing skin, tooth, and duodenum where proliferating and differentiating compartments are readily distinguished. In addition, transient and localized clusterin gene expression was detected in certain morphogenetically active epithelia. In the lung, abundant gene transcripts were detected in cuboidal epithelial cells of the terminal lung buds during branching morphogenesis, and in the kidney, clusterin gene expression in the epithelial cells of comma and S-shaped bodies coincided with the process of polarization. Our results demonstrate the in vivo expression of the clusterin gene by differentiating epithelial cells during murine embryogenesis, and provide novel evidence suggesting that clusterin may be involved in the differentiation and morphogenesis of certain epithelia.

Growth hormone acts on the synthesis and secretion of α-casein in bovine mammary epithelial cells

2005 ◽  
Vol 72 (3) ◽  
pp. 264-270 ◽  
Author(s):  
Kazuhito Sakamoto ◽  
Tokushi Komatsu ◽  
Takuya Kobayashi ◽  
Michael T Rose ◽  
Hisashi Aso ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Epithelial Cells ◽  
Mrna Expression ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Gh Treatment ◽  
Bovine Mammary Epithelial Cells ◽  
Lactogenic Hormone ◽  
Mammary Epithelia

To study the effect of growth hormone (GH) on the functions of mammary epithelia, we examined the effect of GH on the synthesis and secretion of α-casein in a bovine mammary epithelial cell (BMEC) clonal line, which was established from a 26-d-pregnant Holstein heifer. GH receptors (GHR) were observed in the BMEC on the membrane as well as in the cytoplasm. After BMEC were plated onto cell culture inserts, GH stimulated α-casein release in both the presence and absence of the lactogenic hormone complex, which included dexamethasone, insulin and prolactin (DIP). DIP enhanced the effect of GH on α-casein release. Although αs1-casein mRNA expression was not detected in untreated control cells, its expression was observed in BMEC in response to the GH, DIP and GH+DIP treatments. Expression was greater for GH and GH+DIP than for just DIP. Expression of GHR mRNA was increased by DIP treatment, while the mRNA expression was little changed by GH treatment. We conclude that GH acts on BMEC and induces the expression of both the α-casein gene and protein. GHR gene expression was shown to be regulated by DIP and GHR. GHR may be involved in a synergic effect between GH and DIP on casein secretion. These results suggest that GH, in addition to its widely accepted homeorhetic role in vivo, also can act on the mammary parenchyma, and that the effects of GH on mammary epithelial cells could partly account for the clear galactopoietic effect of recombinant bovine GH seen in lactating dairy cows.

scholarly journals The Effect of Growth Hormone on Lipid Accumulation or Maturation in Adipocytes

2016 ◽  
Vol 39 (6) ◽  
pp. 2135-2148 ◽  
Author(s):  
Yuchao Zhang ◽  
Hongsheng Yu ◽  
Peng Gao ◽  
Jicui Chen ◽  
Cong Yu ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Cdna Microarray ◽  
Lipid Accumulation ◽  
Lipid Synthesis ◽  
Epididymal Adipose Tissue ◽  
Gh Treatment ◽  
Gh Secretion ◽  
Expression Of Genes

Background: Adipogenesis of adipocytes includes two stages: initiation and maturation. Growth hormone (GH) secretion is decreased in obese subjects and GH levels are inversely correlated with abdominal fat mass. The effects of growth hormone (GH) on lipids accumulation or maturation of adipocytes remains elusive. Methods: In the present study, effect of GH on lipid accumulation in vitro and in vivo was examined. cDNA microarray, quantitative real time-PCR (qPCR) and western blotting was used to analyze the expression of genes related to adipocyte lipid accumulation or degradation in pre- or mature 3T3-F442A adipocytes treated with GH and in epididymal adipose tissue of C57BL/6 mice administrated with GH. Level of adiponectin in supernatants of cultured F442A adipocytes was determined by enzyme-linked immune-sorbent assay. Results: We found that in 3T3-F442A especially 6 days post initiation of adipogenesis, GH intervention resulted in decreased expression of adipocyte maturation regulators (C/EBPα, PPARγ) and prominent genes related to lipid synthesis such as FAS and FABP, while the expression of UCP1 was markedly enhanced. cDNA microarray analysis and qPCR showed that the expression of SOCS2 and Adipor2 was increased under GH-treatment in mature 3T3-F442A adipocytes. GH treatment increased the mRNA expression of adiponectin and UCP1 in mature adipocytes. The above results were confirmed by in vivo study. Conclusions: GH potentially negatively modulates the maturation and accumulation of lipid in adipocytes.

Thymic hormone containing cells—IX. Steroids in vitro modulate thymulin secretion by human and murine thymic epithelial cells

1988 ◽  
Vol 30 (1-6) ◽  
pp. 479-484 ◽  
Author(s):  
W. Savino ◽  
E. Bartoccioni ◽  
F. Homo-Delarche ◽  
M.Cl. Gagnerault ◽  
T. Itoh ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Thymic Epithelial Cells ◽  
Thymic Hormone

scholarly journals An immunocytochemical study of a rat pituitary multipotential clone.

1978 ◽  
Vol 26 (2) ◽  
pp. 94-97 ◽  
Author(s):  
E P Bowie ◽  
H Ishikawa ◽  
M Shiino ◽  
E G Rennels
Keyword(s):  
Growth Hormone ◽  
General Circulation ◽  
Cell Types ◽  
Hypothalamic Region ◽  
In Vitro System ◽  
Culture Cells ◽  
Rat Pituitary ◽  
Made In

The 2A8 clone, a normal diploid rat anterior pituitary cell strain, was investigated by immunocytochemistry to determine the cell types into which the clonal cells differentiated in vivo and in vitro. The in vivo study was carried out by injecting the 2A8 clone preparation either into the hypothalamic region or under the kidney capsule. After thirty days the implants were removed and studied by immunocytochemistry. In vitro, many prolactin cells and a few growth hormone cells were found. In vivo, however, prolactin, growth hormone, ACTH and TSH cells and gonadotrophs were identified. We concluded that the 2A8 clone was multipotential. Since the gonadotrophs of the implants made in the hypothalamic region were larger and more plentiful than those in the kidney implants, and since gonadotrophs were lacking in the in vitro system, it appeared that the hypophysiotrophic environment was the most conducive to gonadotrophic differentiation and maintenance, and that the factor or factors necessary for cyto-differentiation were apparently present in the general circulation of the rat but absent in the growth medium of our culture cells.

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