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At least 397 records · Page 22Linked to original sources
PubMed2001

Ionic currents in PC12 cells differentiated into neuron-like cells by a cultured-sciatic nerve conditioned medium.

The present work deals with the identification of the ionic currents found in PC12 cells differentiated into neuron-like cells by a 9-11-day cultured-sciatic nerve conditioned medium (CM). PC12 whole-cell currents were measured after chronic exposure to CM. The results obtained in these CM-treated cells reveal that the functional expression of Ca(2+) currents is increased, that Na+ currents are not affected, and that a transient K+ current and a K+ delayed rectifier (K+ dr) current are increased. The combination of nifedipine and omega-conotoxin GVIA (omega-CgTX) does not block completely the increased functional expression of the Ca(2+) current. The remaining current is blocked by omega-agatoxin TK indicating that P/Q-type channels are additionally contributing to the increase in Ca(2+) current. NGF-treated PC12 cells, used as positive controls, confirm that NGF increases the expression of voltage-dependent Na+ currents and of Ca(2+) currents. In addition, we found that NGF also increases a K+ dr-type current in these cells. The results obtained with the CM might be due to a molecule or a mixture of molecules released into the medium by the 9-11-day cultured sciatic nerves.

Animals↗
PubMed1987

Increased density of class I major histocompatibility complex antigens and decreased density of T-cell differentiation antigens in the early stages of T-cell activation.

Major histocompatibility complex (MHC) antigens and T-cell differentiation antigens on activated T cells play a central role in T-cell interactions. In the present study, we have analyzed time courses of both quantity and density of the T-cell differentiation antigens, CD3 (T3), CD4 (T4), and CD8 (T8), as well as MHC antigens, on the cell surface of T cells, and made correlated measurements of DNA content with the surface antigen quantity as well with RNA content and cell size following activation of T cells by phytohemagglutinin. We found that the quantity and density of class I MHC antigens increase within 24 hr following activation and then decrease, while the quantity and density of the T-cell differentiation antigens decrease within 24 hr following activation, which suggests that T-cell recognition involving class I MHC gene products occurs at an early stage of T-cell activation. Class II MHC antigens can be detected on more than 40% of T cells as the expression of the T-cell differentiation antigens increases much later in the response. Cell cycle studies demonstrated that the density of class I MHC, CD3, CD4, and CD8 antigens was greater in G0/G1 phase cells than G2 phase cells at all times tested during T-cell activation. Our findings suggest that T cells demonstrate a differential regulation in expression of MHC and T-cell differentiation antigens following activation which may reflect their role in cellular interactions.

Antigens, Differentiation, T-Lymphocyte↗
PubMed2000

Identification of a precursor to phosphatidyl choline-specific B-1 cells suggesting that B-1 cells differentiate from splenic conventional B cells in vivo: cyclosporin A blocks differentiation to B-1.

The origin of B-1 cells is controversial. The initial paradigm posited that B-1 and B-2 cells derive from separate lineages. More recently it has been argued that B-1 cells derive from conventional B cells as a result of T-independent Ag activation. To understand B-1 cell differentiation, we have generated Ig transgenic (Tg) mice using the H and L chain genes (VH12 and Vkappa4) of anti-phosphatidyl choline (anti-PtC) B cells. In normal mice anti-PtC B cells segregate to B-1. Segregation is intact in VH12 (6-1) and VH12/Vkappa4 (double) Tg mice that develop large numbers of PtC-specific B cells. However, if B-1 cell differentiation is blocked, anti-PtC B cells in these Tg mice are B-2-like in phenotype, suggesting the existence of an Ag-driven differentiative pathway from B-2 to B-1. In this study, we show that double Tg mice have a population of anti-PtC B cells that have the phenotypic characteristics of both B-2 and B-1 cells and that have the potential to differentiate to B-1 (B-1a and B-1b). Cyclosporin A blocks this differentiation and induces a more B-2-like phenotype in these cells. These findings indicate that these cells are intermediate between B-2 and B-1, further evidence of a B-2 to B-1 differentiative pathway.

Animals↗
PubMed1998

Deficient interleukin-10 production by neonatal T cells does not explain their ineffectiveness at promoting neonatal B cell differentiation.

Neonatal T cells are poor promoters of Ig secretion by neonatal B cells. Since IL-10 has been shown to play a role in B cell differentiation, we investigated the relationship of IL-10 production by neonatal T cells and their ability to provide B cell help. Neonatal CD4+(CD8-) T cells and adult naive CD4+ (CD8-/CD45RO-) T cells activated with immobilized anti-CD3 produced consistently less IL-10 than adult memory CD4+(CD8-/CD45RA-) T cells. Production of IL-10 by adult and neonatal T cells was dependent on IL-2, but was unaffected by supplemental IL-4. Despite diminished IL-10 production, supplemental IL-10 increased neonatal T cell-dependent Ig secretion only modestly, but did not increase Ig heavy chain isotype switching. This contrasted with the ability of IL-10 to enhance the secretion of all Ig isotypes by adult B cells stimulated in the presence of either IL-2 or IL-4. These results suggest that IL-10 can promote T cell-dependent Ig secretion but not Ig heavy chain isotype switching by neonatal B cells. However, deficient IL-10 production alone does not account for the poor ability of neonatal T cells to support neonatal B cell Ig production.

Adult↗
PubMed2006

Regulation of human T helper cell differentiation by antigen-presenting cells: the bee venom phospholipase A2 model.

Whereas some individuals develop immunity to bee sting and mount protective IgG4- mediated antibody responses to bee venom phospholipase A2 (PLA), others produce large amounts of PLA-specific IgE antibodies and become allergic to this, otherwise, innocuous antigen. PLA-specific IgE responses are the result of imbalanced T helper (Th)2-cell differentiation. There are multiple mechanisms driving the differentiation of naive CD4+ T cells into Th1- or Th2-cell phenotypes. Most of them are linked to the conditions occurring during initial or repeated encounters with the allergen, in the context of an antigen-presenting cell (APC). The different types of APC and their availability to display particular cytokine production profiles, pattern recognition receptors, costimulatory molecules and specific HLA haplotypes are key determinants for human Th1- and Th2-cell polarization.

Animals↗
PubMed2003

Differential involvement of protein kinase C in human promyelocytic leukemia cell differentiation enhanced by artemisinin.

Artemisinin, a sesquiterpene lactone endoperoxide that exists in several medicinal plants, is a well-known anti-malarial agent. In this report, we investigated the effect of artemisinin on cellular differentiation in the human promyelocytic leukemia HL-60 cell culture system. Artemisinin markedly increased the degree of HL-60 leukemia cell differentiation when simultaneously combined with low doses of 1 alpha,25-dihydoxyvitamin D(3) [1,25-(OH)(2)D(3)] or all-trans retinoic acid (all-trans RA). Artemisinin by itself had very weak effects on the differentiation of HL-60 cells. Cytofluorometric analysis and cell morphologic studies indicated that artemisinin potentiated 1,25-(OH)(2)D(3)-induced cell differentiation predominantly into monocytes and all-trans RA-induced cell differentiation into granulocytes, respectively. Extracellular-regulated kinase (ERK) inhibitors markedly inhibited HL-60 cell differentiation induced by artemisinin in combination with 1,25-(OH)(2)D(3) or all-trans RA, whereas phosphatidylinositol 3-kinase (PI3-K) inhibitors did not. Particularly, protein kinase C (PKC) inhibitors inhibited HL-60 cell differentiation induced by artemisinin in combination with 1,25-(OH)(2)D(3) but not with all-trans RA. Artemisinin enhanced PKC activity and protein level of PKC beta I isoform in only 1,25-(OH)(2)D(3)-treated HL-60 cells. Taken together, these results indicate that artemisinin strongly enhanced 1,25-(OH)(2)D(3)- and all-trans RA-induced cell differentiation in which PKC is differentially involved in arteminisin-mediated enhancement of leukemia cell differentiation.

Artemisinins↗
PubMed2004

Lymphotoxin-mediated regulation of gammadelta cell differentiation by alphabeta T cell progenitors.

The thymus gives rise to two T cell lineages, alphabeta and gammadelta, that are thought to develop independently of one another. Hence, double positive (DP) thymocytes expressing CD4 and CD8 coreceptors are usually viewed simply as progenitors of CD4+ and CD8+ alphabeta T cells. Instead we report that DP cells regulate the differentiation of early thymocyte progenitors and gammadelta cells, by a mechanism dependent on the transcription factor RORgt, and the lymphotoxin (LT) beta receptor (LTbetaR). This finding provokes a revised view of the thymus, in which lymphoid tissue induction-type processes coordinate the developmental and functional integration of the two T cell lineages.

Animals↗
PubMed1985

Recombinant gamma-interferon and lipopolysaccharide enhance 1,25-dihydroxyvitamin D3-induced cell differentiation in human promyelocytic leukemia (HL-60) cells.

The induction of cell differentiation by a combination of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], recombinant gamma-interferon (rec gamma-IFN), and a lipopolysaccharide from E. coli (LPS) was studied in a clonal population (clone-9) of human promyelocytic HL-60 leukemia cells in vitro. Treatment of clone-9 cells with 10(-9) to 10(-7)M 1,25-(OH)2D3 yielded a macrophage cell differentiation. The addition of 10 or 100 U/ml of gamma-IFN and 2 or 10 micrograms/ml LPS caused a further increase in expression of the different differentiation markers. The most pronounced effects involved increases in cell attachment to the surface of tissue-culture Petri dishes and in lysozyme, nonspecific esterase, and cytolytic activities. The combined treatment with 1,25-(OH)2D3 and rec gamma-IFN and LPS also caused an increase in the percent of multinucleated giant cells. These results indicate the effectiveness of combining different agents in inducing cell differentiation in HL-60 cells. A similar approach may be useful in controlling myeloid leukemias in vivo.

24,25-Dihydroxyvitamin D 3↗
PubMed1984

Induction of T-cell differentiation.

T cell development can be viewed as precursor cells migrating from yolk-sac and liver in the embryo, and bone marrow and spleen in the adult to the thymic cortex as functionally immature T-cells, and to the medulla where they acquire immunological function, and finally joining the pool of T-cells in the blood lymphoid system and spleen. Several cell surface markers were used to study these processes, such as TL, Ly-1, Ly-2/3, Qa-1, and I-J. Using these cell surface markers combined with biologically active reagents in functional tests in vitro, several conclusions can be drawn to illustrate these differentiation steps. 1) T cell precursors are precommitted and can be separated from other hematopoietic stem cells. 2) During induction of prothymocytes several new unlinked gene products are expressed. 3) Thymopoietin is a physiological inducer. 4) This induction to express new surface markers requires transcription and translation but is independent of DNA synthesis, at least according to the action of metabolic inhibitors. 5) Surface phenotypes and function of cells are coordinately programmed. 6) Most Ly1 and Ly23 cells, if not all, are derived from Ly123 precursor cells. 7) Acquisition of new surface phenotype precedes new functional expression, supporting the hypothesis that the differentiation process consists in pre-mitotic expression of a gene set for phenotype, and postmitotic expression of a set for function. 8) The differentiation steps require cell-cell interaction, either by direct contact or by soluble factors within the same T-cell linkage.

Animals↗
PubMed2003

Constitutively active mutant D816VKit induces megakayocyte and mast cell differentiation of early haemopoietic cells from murine foetal liver.

Mutations of Kit at position D816 have been implicated in mastocytosis, acute myeloid leukaemia and germ cell tumours. Expression of this mutant Kit in cell lines results in factor-independent growth, differentiation and increased survival in vitro and tumourigenicity in vivo. Mutant D816VKit and wild-type Kit were expressed in murine primary haemopoietic cells and grown in stem cell factor (SCF) or the absence of factors. Expression of D816VKit did not lead to transformation as assessed by a colony assay, but resulted in enhanced differentiation of cells when compared to control cells. D816VKit induced an increase in the number of cells differentiating along the megakaryocyte lineage in the absence of factors. SCF had an added effect with an increase in differentiation of mast cells. Expression of wild-type Kit in the presence of SCF also failed to cause transformation and induced differentiation of mast cells and megakaryocytes. We conclude that constitutive expression of D816VKit in primary haemopoietic cells is not a sufficient transforming stimulus but leads to the survival and maturation of cells whose phenotype is influenced by the presence of SCF.

Antigens, Nuclear↗
PubMed2005

Tumor skewing of CD34+ cell differentiation from a dendritic cell pathway into endothelial cells.

Patients and animals bearing tumors have increased levels of CD34(+) progenitor cells, which are capable of developing into dendritic cells. However, addition of medium conditioned by murine Lewis lung carcinoma cells increases the cellularity of the CD34(+) cell cultures and redirects their differentiation into endothelial cells. The resulting cells resemble endothelial cells phenotypically as well as functionally by their capacity to reorganize into cord structures. Mechanisms by which tumors induced the increased cellularity and skewing toward endothelial cells were examined. Tumor-derived VEGF contributed to the increase in cellularity, but not to the redirection of differentiation. Differentiation into endothelial cells was blocked with sTie-2, suggesting tumor-derived angiopoietins in skewing differentiation. These studies show the capacity of tumors to skew progenitor cell development toward endothelial cells and define the mediators that contribute to endothelial cell development.

Animals↗
PubMed1991

Hormonal control of Leydig cell differentiation.

Leydig cell progenitors contain significant concentrations of androgen receptors. When the metabolism of DHT to 3 alpha-DIOL is blocked, DHT stimulates testosterone production by Leydig cell progenitors, most probably via an androgen receptor dependent mechanism. Rapid metabolism by 3 alpha-HSD may limit the potency of exogenous DHT to stimulate differentiation of Leydig cell progenitors in vitro. Insulin-like growth factor-I enhances androgen production by purified immature Leydig cells. The elevated sensitivity of immature Leydig cells versus adult Leydig cells to IGF-I stimulation indicates that this peptide hormone has a role in their differentiation during puberty.

Androgens↗
PubMed1999

Regulation of T helper cell differentiation by respiratory tract dendritic cells.

Studies on dendritic cells (DC) of the respiratory and gastric mucosae have identified an extensive network of cells that represent the predominant antigen-presenting cell type at these sites. Under steady-state conditions, respiratory tract DC (RTDC) are specialized for antigen uptake and spontaneously migrate to local lymph nodes, although in vivo transfer studies have shown that the T-cell priming activity of these cells is restricted to low-level, Th2-skewed responses. Following exposure to inflammatory stimuli, the migration of RTDC to lymph nodes is accelerated and is associated with a rapid and dramatic increase in the ability of these cells to induce both Th1- and Th2-dependent immunity. Under normal circumstances, however, responsiveness of epithelial RTDC to maturation stimuli is regulated by locally produced micro-environmental factors, including pro-inflammatory cytokines, reactive oxygen species and prostanoids. These studies have led to a greater understanding of airway DC function and their role in T helper cell differentiation and provide the basis for future studies to determine the role of the cells in the aetiology and pathogenesis of respiratory immunoinflammatory disorders.

Animals↗
PubMed1999

alpha-catenin-deficient F9 cells differentiate into signet ring cells.

It has been demonstrated that alpha-catenin is frequently lost in diffuse type adenocarcinomas. We have isolated alpha-catenin-deficient mouse teratocarcinoma F9 cells by gene targeting. Wild-type F9 cell aggregates cultured in the presence of retinoic acid differentiated into embryoid bodies with an outer layer of epithelial cells. In contrast, cell aggregates of alpha-catenin-deficient cells did not develop outer layers under the same conditions. The outer surface cells of alpha-catenin-deficient cell aggregates, however, differentiated into epithelial cells as determined by their expression of epithelial marker proteins. These differentiated cells scattered from aggregates and showed signet ring cell morphology, which is frequently observed in diffuse type adenocarcinomas. We have provided clear evidence that a single mutation in the alpha-catenin gene may be a direct cause not only of the scattered properties of cells but also of signet ring cell formation in diffuse type adenocarcinoma.

Animals↗
PubMed1997

Overexpression of human stem cell factor impairs melanocyte, mast cell, and thymocyte development: a role for receptor tyrosine kinase-mediated mitogen activated protein kinase activation in cell differentiation.

Stem cell factor (SCF) is synthesized as both soluble (S) and membrane-associated (MA) proteins. Indirect insight into the function of MA and S isoforms of SCF has come from studies performed in Steel (Sl) mutant mice. However, the physiologic role(s) of these two isoforms remain unknown. In an attempt to better understand the in vivo role of c-kit/SCF interactions on various cell lineages, transgenic mice were generated that overexpress MA isoform of human SCF (hSCF). In murine cells, hSCF behaves as an antagonist to normal SCF function, due to interference with the interaction between endogenous murine SCF and its receptor, c-kit, encoded by the dominant white spotting (W) gene. Mice expressing the hSCF transgene display a variety of phenotypic abnormalities, which are accentuated when combined with W alleles. Here we show that mice homozygous for the hSCF transgene demonstrate a coat color deficiency seen in some mice homozygous for mild W alleles. Specifically, homozygous hSCF transgenic mice (hSCF220) display a pronounced forehead blaze, with additional white spots over the cervical region, as well as a very large belly spot. Doubly heterozygous animals that carry both a mutated W allele and the hSCF transgene also display an unusual pigment defect and a dramatic reduction in the number of dermal mast cells. Furthermore, overexpression of MA hSCF in the thymus results in abnormal thymocyte differentiation and proliferation, which is associated with reduced mitogen activated protein (MAP) kinase activation. Thus, MAP kinase activation by a receptor tyrosine kinase, such as c-kit, may be critical for the differentiation of thymocytes in vivo.

Animals↗
PubMed2004

Retinoic acid regulates cell cycle progression and cell differentiation in human monocytic THP-1 cells.

All-trans-retinoic acid (RA), a natural metabolite of retinol, carries out most of the biological activities of vitamin A and is required for normal growth, cell differentiation, and immune functions. In the present studies, THP-1 human monocytes were used to investigate the mechanisms by which RA may regulate progression through the G1/S phase of the cell cycle. Physiological concentrations of all-trans-RA reduced the levels of cyclin E mRNA by 6 h and reduced cyclin E protein in a dose- and time-dependent manner. Similar reductions were observed for the retinoic acid receptor RARalpha and RXRalpha proteins. Concomitantly, RA increased the level of the cyclin-dependent kinase inhibitor p27 (Kip-1). The levels of retinoblastoma mRNA and protein (pRb) were also increased, while the proportion of hyperphosphorylated (phosphoserine 807/811) pRb was markedly reduced. Overall, RA increased the functionality of pRb as an inhibitor of cell cycle progression. Furthermore, RA reduced the binding activity of the transcription factor E2F to its core DNA element. Retinoic acid-induced changes in cell cycle-related proteins occurred in 4-6 h, including reduced cyclin E expression in bromodeoxyuridine (BrdU)-labeled cells, before the onset of cell differentiation as indicated by an increase in the percentage of G1 phase cells and a reduction in S phase cells at 24 h. The expression of CD11b, a cell surface marker of macrophage-like differentiation was increased by RA, as was phagocytic activity. The multiple effects of RA on cell cycle progression may help to explain its well-documented ability to induce the differentiation of THP-1 cells, and thereby to enhance macrophage-like immune functions.

CD11b Antigen↗
PubMed1978

Co-regulation of type C RNA virus production and cell differentiation in myeloid leukemic cells.

Mouse myeloid leukemic cells which differ in their competence to be induced to differentiate by the normal macrophage- and granulocyte-inducing protein MGI have been used to study the relationship between type C RNA virus production and myeloid cell differentiation. Clones which can be induced by MGI to form Fc and C3 rosettes, to synthesize and secrete lysozyme and to differentiate to mature macrophages and granulocytes (MGI+D+) were induced by MGI to produce higher amounts of type C virus. Clones (MGI+D-) that were less inducible by MGI for Fc and C3 rosettes and lysozyme and were not induced to from mature cells were also less inducible higher virus production. In both types of clones, the increased virus production induced by MGI preceded the induction of rosettes and lysozyme. Clones that were not induced by MGI for rosettes or lysozyme (MGI-D-) showed little or no enhancement of virus production. MGI did not affect virus production in erythroleukemic cells, and erythropoietin did not affect virus production in the myeloid leukemic cells. Dexamethasone, lipopolysaccharide, dimethylsulfoxide and low concentrations of actinomycin D can induce some differentiation-associated properties in some of the clones. With these compounds, there was also a direct relationship between the enhancement of virus production and induction of differentiation-associated properties. Virus released from the three types of clones before or after treatment with MGI or dexamethasone was identified as N-tropic. The enhancement of virus production, as measured by reverse transcriptase activity, was accompanied by an increase in the amount of the viral protein p30, and interferon, which idd not inhibit the induction of differentiation in the myeloid leukemic cells, also did not prevent the increase in the amount of p30. After the early enhancement of virus production associated with the induction of differentiation, a shut-off of virus production occurred in the mature cells induced by MGI in MGI+D+ clones, whereas clones that did not differentiate to mature cells continued to produce virus. The results indicate that enhancement of virus production appears to be an early step in the induction of differentiation. Once induction has occurred, the lack of virus production in the mature cells suggest that a subsequent shut-off of virus production may be required for the completion of differentiation to mature cells. This relationship between cell differentiation and virus production suggests that type C virus has a regulatory role in myeloid cell differentiation.

Animals↗
PubMed1999

Transcriptional regulation in B cell differentiation.

B cell development is a multistage differentiation process that ultimately generates antibody-secreting plasma cells. This model developmental pathway is governed by a choreographed pattern of expression from genes encoding stage and lineage-specific proteins. This is achieved by the interaction of distinct transcription factors with regulatory elements, placing these proteins in a central position in B cell ontogeny. The importance of distinct transcription factors is also supported by the notion that B cell development is disrupted in mice bearing homozygous null alleles of certain factors involved in the control of B-cell-specific genes. In this review we compare and contrast the transcriptional regulation of well-studied B lymphoid restricted genes, on a gene by gene basis, focusing on the functional structure of transcription control regions and interacting transcription factors.

Animals↗