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Results for “Functional differentiation”

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PubMedDate not supplied

Evaluation of proliferation and functional differentiation of LLC-PK1 cells on porous polymer membranes for the development of a bioartificial renal tubule device.

To develop a bioartificial renal tubule system using renal tubular cells and porous polymer membrane hollow fibers, long-term maintenance of a confluent monolayer and the functionally differentiated condition of cells is essential. We examined the proliferation and functional differentiation of LLC-PK1 (Lewis-lung cancer porcine kidney 1) cells on two types of membranes: polysulfone and cellulose acetate. Cell proliferation was significantly higher on the polysulfone membrane than on the cellulose acetate membrane, and was enhanced by coating the membranes with various extracellular matrices. Confluent monolayer formation of cells was observed on matrix-coated polysulfone membrane but not on matrix-coated cellulose acetate membrane within 1 week. Cell proliferation continued for 3 weeks after confluent monolayer formation. Messenger RNA (mRNA) expression of glucose transporters, indicators of the functional differentiation of the LLC-PK1 cells, was observed in the polysulfone and cellulose acetate membrane groups, but was not observed in the nonporous polystyrene plate group under subconfluent conditions. Expression of glucose transporters mRNA was maintained for 3 weeks after confluent monolayer formation. Polysulfone membrane is more suitable than cellulose acetate membrane for a bioartificial renal tubule system with regard to LLC-PK1 cell proliferation. Extracellular matrix coating of the membrane further improves cell proliferation.

Animals↗
PubMed2002

Polycyclic aromatic hydrocarbons affect functional differentiation and maturation of human monocyte-derived dendritic cells.

Polycyclic aromatic hydrocarbons (PAHs) such as benzo(a)pyrene (BP) are environmental carcinogens exhibiting potent immunosuppressive properties. To determine the cellular bases of this immunotoxicity, we have studied the effects of PAHs on differentiation, maturation, and function of monocyte-derived dendritic cells (DC). Exposure to BP during monocyte differentiation into DC upon the action of GM-CSF and IL-4 markedly inhibited the up-regulation of markers found in DC such as CD1a, CD80, and CD40, without altering cell viability. Besides BP, PAHs such as dimethylbenz(a)anthracene and benzanthracene also strongly altered CD1a levels. Moreover, DC generated in the presence of BP displayed decreased endocytic activity. Features of LPS-mediated maturation of DC, such as CD83 up-regulation and IL-12 secretion, were also impaired in response to BP treatment. BP-exposed DC poorly stimulated T cell proliferation in mixed leukocyte reactions compared with their untreated counterparts. In contrast to BP, the halogenated arylhydrocarbon 2,3,7,8-tetrachlorodibenzo-p-dioxin, which shares some features with PAHs, including interaction with the arylhydrocarbon receptor, failed to phenotypically alter differentiation of monocytes into DC, suggesting that binding to the arylhydrocarbon receptor cannot mimic PAH effects on DC. Overall, these data demonstrate that exposure to PAHs inhibits in vitro functional differentiation and maturation of blood monocyte-derived DC. Such an effect may contribute to the immunotoxicity of these environmental contaminants due to the major role that DC play as potent APC in the development of the immune response.

Benzo(a)pyrene↗
PubMed1994

In vivo cytokine expression in the thymus. CD3high human thymocytes are activated and already functionally differentiated in helper and cytotoxic cells.

CD4 and CD8 are expressed on mutually exclusive T cell populations that can recognize peptides bound to class II and class I MHC Ags, respectively. These populations have different functions and are different in their capacity to produce cytokines. In this paper we demonstrate that this functional differentiation occurs at the CD3low- CD3high transitional stage: single positive mature CD4+ thymocytes express IL-2 mRNA in vivo, whereas CD8+ thymocytes primarily express perforin. IL-2, perforin, and IFN-gamma mRNAs were almost absent in CD4+CD8+ CD3low but were clearly detectable in CD4+CD8+ CD3high cells, indicating that these genes are induced at the CD3low- CD3high transitional stage. In contrast, IL-4 mRNA levels were highest in the precursor cells but dropped sharply at the CD3low-CD3high transitional stage. These data are consistent with and link two earlier observations, i.e., that activation occurs at the CD3low-CD3high transition and that functional differentiation in helper and cytotoxic cells is already accomplished in the single positive thymocytes. This activation may reflect positive selection and concomitant functional differentiation into helper and cytotoxic T cells.

Animals↗
PubMed1999

Treatment of human endometrial stromal cells with chorionic gonadotropin promotes their morphological and functional differentiation into decidua.

Human endometrial stromal cells contain luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptors and treatment with highly purified hCG results in an up-regulation of cyclooxygenase-2 (COX-2) gene expression and increased production of prostaglandin (PG) E2. Since PGE2 promotes the differentiation of endometrial stromal cells into decidua, we tested the hypothesis that LH and hCG themselves may promote this process. The results revealed that these hormones can promote morphological as well as functional differentiation. While their action on morphological differentiation did not require the presence of estradiol (E2) and progesterone (P4), they did require them for the functional differentiation. The hCG effect was mimicked by LH, but not by follicle stimulating hormone (FSH), thyroid stimulating hormone (TSH) or alpha and beta subunits of hCG, suggesting that the hCG action was hormone specific and requires the conformation of native hormone. The hCG treatment also increased the steady state PRL mRNA levels. This increase was due to an increase in the transcription rate of the gene rather than a decrease in the degradation of PRL transcripts. In summary, we conclude that hCG and LH can increase the morphological as well as functional differentiation of human endometrial stromal cells into decidua. This is one of the newly discovered actions of LH and hCG that may be important for the implantation of blastocyst and maintenance of pregnancy.

Adult↗
PubMed2006

1alpha,25-Dihydroxyvitamin D3 downmodulates the functional differentiation of Th1 cytokine-conditioned bone marrow-derived dendritic cells beneficial for cytotoxic T lymphocyte generation.

Various dendritic cell subsets are induced from bone marrow cells under different cytokine conditions. We have demonstrated previously that the Th1-cytokine-conditioned bone marrow-derived dendritic cell (BMDC) subset BMDC1 (generated in the presence of granulocyte-macrophage colony-stimulating factor [GM-CSF] + interleukin [IL]-3 + interferon [IFN]-gamma+ IL-12) induces a much stronger type 1 immune response than BMDC0 (GM-CSF + IL-3). In the present study, we investigated the effect of 1alpha,25-dihydroxyvitamine D3 (VitD3), which is a known immunomodulating drug, on the differentiation of BMDC subsets. The addition of VitD3 significantly influenced the functional differentiation of BMDC1 compared with BMDC0. Specifically, the addition of VitD3 greatly decreased the expression levels of MHC class I, CD80, CD40 and leukocyte function-associated antigen (LFA)-1 molecules on BMDC1. In addition, VitD3-treated BMDC1 (VD3-BMDC1) almost completely lost their immunostimulating activity for inducing type 1 immunity and cytotoxic T lymphocyte generation. A failure in the induction of type 1 immunity by VD3-BMDC1 appeared to be due to the following: (i) the expression of co-stimulatory molecules on VD3-BMDC1 was strongly downmodulated compared with BMDC1 generated without VitD3; and (ii) VD3-BMDC1 showed significantly lower mRNA expression of IFN-gamma and IFN-beta, factors that are essential for cytotoxic T lymphocyte induction. VitD3 inhibited the differentiation of functionally competent BMDC1 during the early phase of differentiation but not during the late differentiation period. A possible reason for the inhibition of BMDC1 differentiation by VitD3 is reduced phosphorylation of STAT1 during early differentiation. Taken together, VitD3 strongly suppressed T-cell responses by inhibiting functional differentiation of precursor dendritic cells into functional BMDC1 that are feasible for inducing Th1-dependent cellular immunity.

Animals↗
PubMed1985

Induction of functional differentiation of a human monocytic leukemia cell line (THP-1) by retinoic acid and cholera toxin.

The human monocytic leukemia cell line, THP-1, is induced to differentiate into more functionally mature monocyte (macrophage)-like cells by incubation with retinoic acid at concentrations of 10nM or higher. There is no apparent morphological change accompanying this functional maturation. These induced cells show increases in nitroblue tetrazolium reduction, immunoerythrophagocytosis, hexose monophosphate shunt activity, and 5'-nucleotidase and NAD+-glycohydrolase activities. Prostaglandin E2, dibutyryl cyclic adenosine 3':5'-monophosphate, or T-lymphocyte-derived differentiation-inducing activity, all inactive or less active alone, increase the extent of differentiation of THP-1 in combination with 10nM retinoic acid. THP-1 is also induced to differentiate by 0.1nM or higher concentrations of cholera toxin. Furthermore, 24,24-difluoro-1 alpha,25-dihydroxyvitamin D3 induces less differentiation of THP-1 compared to retinoic acid. Dimethyl sulfoxide and 12-O-tetradecanoylphorbol-13-acetate show no induction of functional differentiation. THP-1 thus joins the list of leukemic myelomonocytic cell lines (e.g., the promyelocytic HL-60 and the monoblast-like U-937) that are blocked at a relatively late stage of maturation and which differentiate in response to retinoic acid.

5'-Nucleotidase↗
PubMed1996

Repression of transforming growth factor beta 1 protein by antisense oligonucleotide-induced increase of adrenal cell differentiated functions.

Transforming growth factor beta 1 (TGF beta 1) is a potent inhibitor of several differentiated functions in bovine adrenal fasciculata cells (BAC). In addition, these cells express and secrete this factor. To determine whether this peptide plays an autocrine role in BAC, cells were transfected with 10 microM unmodified sense (SON) or antisense (AON) oligonucleotide complementary to the translation initiation region of the TGF beta 1 mRNA in an attempt to inhibit TGF beta 1 protein synthesis. We investigated first, the cellular uptake, the stability, and the intracellular distribution of 32P-labeled TGF beta 1 AON and SON; and second, the effects of both oligonucleotides on BAC specific functions. We have demonstrated that in BAC, the TGF beta 1 AON uptake reached a plateau after 8 h of transfection (16% of the radioactivity added) and remained fairly constant for at least 24 h. In contrast, the uptake of TGF beta 1 SON reached a plateau after 2 h of transfection (8% of the radioactivity added), remained stable for only 3 h, and then declined. After 8 h of transfection, followed by 44 h of culture without oligonucleotides, the intracellular level of TGF beta 1 AON was still high with about 8% of the radioactivity added, whereas that of TGF beta 1 SON represented only 1.2%. Moreover, AON was present in the cytoplasmic and nuclear fractions, and it was hybridized in both compartments. However, TGF beta 1 SON was present mainly in the cytoplasmic fraction where it was not hybridized. Neither TGF beta 1 AON nor SON modified TGF beta 1 mRNA levels; however, TGF beta 1 AON, but not SON, caused the disappearance of TGF beta 1 immunoreactivity inside the cells. Finally, the steroidogenic responsiveness of BAC transfected with TGF beta 1 AON increased about 2-fold, and this was associated with a 2-fold increase of the mRNA levels of both cytochrome P450 17 alpha-hydroxylase and 3 beta-hydroxysteroid dehydrogenase. Neither TGF beta 1 SON nor a scrambled oligonucleotide containing the same number of G nucleotides as TGF beta 1 AON had any effect on these parameters. Thus, these studies demonstrate that TGF beta 1 has an autocrine inhibitory effect on BAC differentiated functions, an effect that can be overcome by TGF beta 1 AON.

Adrenal Cortex↗
PubMed1997

Conditionally immortalized cell lines with differentiated functions established from temperature-sensitive T-antigen transgenic mice.

A variety of cell lines with differentiated functions are required to study tissue functions at cellular and molecular levels. Using transgenic mice harbouring ubiquitously expressing the temperature-sensitive T-antigen (ts T-antigen) gene of simian virus 40 (SV40), many cell lines were generated. The properties of these established lines suggested that their growth was dependent on T-antigen, and that they retained some of the differentiated functions of each particular tissue. A possible use of these cell lines for tissue functions in vitro is discussed.

Animals↗
PubMed1986

Expression of differentiated functions in kidney epithelial cell lines.

The expression of differentiated functions in long-term cell lines MDCK and LLC-PK1 derived from renal epithelia is briefly summarized. Topics include differentiated transport properties and enzymatic functions expressed by these cell lines, modulation of a differentiated phenotype by exogenous inducers, substratum and cell-cell contact, and possible mechanisms of inducer action.

Acetamides↗
PubMedDate not supplied

Further evidence of functional differentiation within biceps brachii.

This study investigated whether the two heads of Biceps Brachii could be functionally differentiated during rapid supination movements with different degrees of elbow flexion, shoulder axial rotation and load. Surface electromyograms, recorded from the long and short heads of Biceps Brachii, were utilised to identify changes in the intensity of muscle contraction. Based upon an analysis of sixteen subjects, the results indicated that joint position (muscle length), but not load, significantly (p < 0.05) influenced the relationship between the contraction intensities of the two heads. Specifically, increasing the length of the Biceps Brachii promoted increased activation of the long head in relation to the short head in producing rapid supination motions. It was concluded that functional differentiation within the two heads of Biceps Brachii was present in motions involving its distal insertion.

Adolescent↗
PubMed1996

Fractional differentiability of nowhere differentiable functions and dimensions.

Weierstrass's everywhere continuous but nowhere differentiable function is shown to be locally continuously fractionally differentiable everywhere for all orders below the "critical order" 2-s and not so for orders between 2-s and 1, where s, 1<s<2 is the box dimension of the graph of the function. This observation is consolidated in the general result showing a direct connection between local fractional differentiability and the box dimension/local Holder exponent. Levy index for one dimensional Levy flights is shown to be the critical order of its characteristic function. Local fractional derivatives of multifractal signals (non-random functions) are shown to provide the local Holder exponent. It is argued that Local fractional derivatives provide a powerful tool to analyze pointwise behavior of irregular signals. (c) 1996 American Institute of Physics.

Journal Article↗
PubMed1990

Phenotypical and functional differentiation of CD4+ CD45RA+ human T cells following polyclonal activation.

Human CD4+ T cells differ in their expression of the leucocyte common antigen. Antibodies detecting certain forms (CD45RA and CD45RO) of this antigen have been used to identify and isolate subpopulations of the CD4+ T cells. These isolated subsets have been shown to have different abilities concerning lymphokine production and provision of help to B cells for Ig production. When these T-cell subsets were activated in vitro with polyclonal activators, the production. When these T-cell subsets were activated in vitro with polyclonal activators, the CD45RA+ cells lost this marker and gained the expression of CD45RO. This was true for all mitogens used in this report, i.e. accessory cell-dependent stimulation with SEA and accessory cell-independent activation with PMA or PHA. A correlation between proliferation and differentiation was observed, but this was probably not causative as stimulation with PMA in the absence of DNA synthesis resulted in the acquisition of CD45RO and loss of the CD45RA antigen. Moreover, cells proliferating vigorously for long periods of time expressed both markers at significant levels, which suggests that proliferation did not automatically result in complete loss of the CD45RA marker. The phenotypical differentiation was associated with a functional differentiation which induced the stimulated cells' ability to act as helper cells for Ig production and to produce gamma interferon (IFN-gamma). The results obtained in this study support the contention that the CD45RA+ cells are precursors of the CD45RO+ cells and that the two subsets represent different maturational stages of the same lineage.

Antigens, Differentiation↗
PubMed1989

Cultivation of adult rat hepatocytes on 3T3 cells: expression of various liver differentiated functions.

Adult rat hepatocytes were maintained in culture for at least 1 month without losing the expression of their differentiated functions; they were cultured on lethally treated 3T3 fibroblasts inoculated at 35,000 cells/cm2 with medium containing 10-25 micrograms/ml hydrocortisone. Hepatocytes showed their typical morphology; they formed bile canaliculi, microvilli, and intercellular junctions with desmosomes and nexus; some formed structures that may resemble the perisinusoidal space of Disse. In addition, they showed DNA synthesis and expressed some liver-specific functions. They synthesized albumin and other proteins, which were exported to the culture medium. Like parenchymal liver cells in vivo, de novo fatty acid synthesis and esterification took place, and more than 80% of the lipids synthesized by the hepatocytes were secreted into the medium as triglycerides; they also showed cytochrome-P450 activity that was inducible with phenobarbital, suggesting that the hepatocytes have the capacity to metabolize drugs. These culture conditions allow the study of various hepatocyte differentiated functions, and they may provide the means to analyze the effect on liver of hormones, viruses and hepatotoxic chemicals and drugs; they may also indicate conditions adequate for serial growth of hepatocytes.

Animals↗
PubMed2006

GO-Diff: mining functional differentiation between EST-based transcriptomes.

BACKGROUND: Large-scale sequencing efforts produced millions of Expressed Sequence Tags (ESTs) collectively representing differentiated biochemical and functional states. Analysis of these EST libraries reveals differential gene expressions, and therefore EST data sets constitute valuable resources for comparative transcriptomics. To translate differentially expressed genes into a better understanding of the underlying biological phenomena, existing microarray analysis approaches usually involve the integration of gene expression with Gene Ontology (GO) databases to derive comparable functional profiles. However, methods are not available yet to process EST-derived transcription maps to enable GO-based global functional profiling for comparative transcriptomics in a high throughput manner. RESULTS: Here we present GO-Diff, a GO-based functional profiling approach towards high throughput EST-based gene expression analysis and comparative transcriptomics. Utilizing holistic gene expression information, the software converts EST frequencies into EST Coverage Ratios of GO Terms. The ratios are then tested for statistical significances to uncover differentially represented GO terms between the compared transcriptomes, and functional differences are thus inferred. We demonstrated the validity and the utility of this software by identifying differentially represented GO terms in three application cases: intra-species comparison; meta-analysis to test a specific hypothesis; inter-species comparison. GO-Diff findings were consistent with previous knowledge and provided new clues for further discoveries. A comprehensive test on the GO-Diff results using series of comparisons between EST libraries of human and mouse tissues showed acceptable levels of consistency: 61% for human-human; 69% for mouse-mouse; 47% for human-mouse. CONCLUSION: GO-Diff is the first software integrating EST profiles with GO knowledge databases to mine functional differentiation between biological systems, e.g. tissues of the same species or the same tissue cross species. With rapid accumulation of EST resources in the public domain and expanding sequencing effort in individual laboratories, GO-Diff is useful as a screening tool before undertaking serious expression studies.

Animals↗
PubMed2004

Molecular pathology of the pituitary. Development and functional differentiation of pituitary adenomas.

This review article describes functional differentiation of the pituitary cells and pituitary adenomas with special emphasis on transcription factors and co-factors. Human pituitary adenomas generally follow the combination of transcription factors and co-factors, which are similar to those of physiologic anterior pituitary cells. On very rare occasions, the single pituitary adenoma produces two hormones, which belong to different cell lineage 'trans-cell lineage'. Basic mechanism for this was considered to be 'aberrant expression' of transcription factors, i.e. NeuroD1 and Pit-1. This was experimentally supported by the induction of GH (mRNA and protein) in AtT-20 cells by transfecting Pit-1 gene. Various mechanisms have been reported for the experimental pituitary oncogenesis. Among these, GHRH has been emphasized as one of oncogenic factors for both human GHomas as well as in the transgenic animals.

Adenoma↗
PubMed1963

Heritability and control of differentiated function in cultured cells.

An established tissue culture cell line which retains a differentiated function in vitro is described. The cell line is of connective tissue origin, and its characteristic property is the synthesis and secretion of acid mucopolysaccharides, mainly hyaluronic acid. This differentiated cell function, the activity of which depends on continuous gene action, was found to be possessed by each of eleven clonal substrains, and is therefore a genetically heritable cell character. Rate of acid mucopolysaccharide biosynthesis falls sharply under the influence of the environmental conditions existing in crowded cultures, and this rate also declines if protein synthesis is directly inhibited with puromycin. Environmental modification of a differentiated product of gene action is thus illustrated in this study.

Cell Line↗
PubMed1995

Modulation of normal mammary epithelial cell proliferation, morphogenesis, and functional differentiation by retinoids: a comparison of the retinobenzoic acid derivative RE80 with retinoic acid.

The ability of retinoids to modulate the proliferation as well as the morphological and functional differentiation of normal mammary epithelial cells isolated from pubescent female virgin rats was evaluated in serum-free primary culture. The retinobenzoic acid derivative RE80, present continuously or for only a limited time in culture, inhibited proliferation with an IC50 of less than 10(-10) M. In contrast, all-trans-retinoic acid (RA) inhibited proliferation with an IC50 of approximately 10(-8) M. In addition to effects on proliferation, RE80 and RA stimulated end bud colonies to differentiate to lobular alveolar colonies, inhibited alveolar budding, and suppressed the outgrowth of squamous colonies. Both retinoids also markedly stimulated functional differentiation, as assessed by accumulation of the major milk protein casein, and stimulated the synthesis of a approximately 73- to 74-kilodalton protein identified as a member of the transferrin family. Moreover, both retinoids stimulated cell death in the differentiated cell population. RE80 was approximately 100-fold more potent than RA for all of these effects. These data suggest that several mechanisms may contribute to the chemopreventive and/or therapeutic efficacy of retinoids in breast cancer, including inhibition of proliferation, stimulation of cell death, and/or induction of differentiation.

Animals↗