Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Because the pulmonary alveolar space is both the site of gas exchange for respiration and a portal of entry for foreign antigen, immunologic interactions within that space must be meticulously controlled. Alveolar epithelial cells are ideally situated to play a role in immune regulation within the alveolar space. We have used A549 cells, a cell line that is derived from a human alveolar cell carcinoma and that has been used as a model for alveolar type II epithelial cells, to examine the potential role of alveolar epithelial cells in local pulmonary immune regulation. Medium conditioned by confluent monolayers of A549 cells suppressed proliferation by human peripheral blood mononuclear cells (PBMC) stimulated with lectin, anti-CD3 antibodies, calcium ionophore and phorbol ester, or in a mixed leukocyte reaction. PBMC that had been incubated in and then removed from A549-conditioned medium went on to proliferate normally. Because the suppressive effect was abrogated by heating or acidification and was not blocked by neutralizing antibody to transforming growth factor-beta 1, this effect could not be attributed to transforming growth factor-beta. The factor mediating this effect has an approximate molecular weight of 70,000 D by gel filtration chromatography. Nonalveolar, pulmonary carcinoma cell lines did not exert this immunosuppressive influence nor did the alveolar epithelial cells inhibit proliferation by the transformed, Jurkat, T-cell line. Cell cycle analysis demonstrated that PBMC exposed to A549 cell-conditioned medium failed to enter S phase after mitogen stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1992 Jun
PMID:A factor secreted by a human pulmonary alveolar epithelial-like cell line blocks T-cell proliferation between G1 and S phase. 159 Oct 14

The vascular cell responses to the type 1, 2, and 3 isoforms of transforming growth factor-beta (TGF-beta 1, TGF-beta 2, TGF-beta 3) were studied using bovine aortic endothelial (BAECs) and smooth muscle cells (BASMC3) as well as rat epididymal fat pad microvascular endothelia (RFCs). Three distinct bioassays indicated that TGF-beta elicits results that do not differ significantly from those of the TGF-beta 1 isoform in all three cell populations. These assays are: inhibition of proliferation, cell migration, and neovascularization. By contrast the cellular responses to TGF-beta 1 and TGF-beta 3 differed from those to TGF-beta 2. Three distinct receptor assays revealed the presence of type I and type II TGF-beta 1 cell surface binding proteins on BAECs, BASMCs, and RFCs. Experimentation to decipher cell surface binding by the different isoforms revealed that iodinated TGF-beta 1 bound to the surface of all three vascular cell types can be competed off in similar fashion by either TGF-beta 1 or TGF-beta 3; however, competition with TGF-beta 2 produced unique binding profiles dependent on the cell type examined. The ratios of type I to type II TGF-beta receptors in these three vascular cell types vary from 1:1 in BAECs to 1.5:1 in RFCs to 3:1 in BASMCs and can be correlated with the differences noted in cellular responses to TGF-beta 1 and TGF-beta 2 in proliferation, migration, and in vitro angiogenic assays.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Reprod Dev 1992 Jun
PMID:Modulation of vascular cell behavior by transforming growth factors beta. 163 50

Replicative DNA synthesis, as measured by thymidine incorporation, has been measured in rat uterine cells in primary culture in response to growth factors. Insulin, insulin-like growth factor-I (IGF-I), multiplication-stimulating activity (MSA) and platelet-derived growth factor (PDGF) stimulated DNA synthesis, while estradiol, epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta), basic fibroblast growth factor (bFGF) and relaxin did not stimulate or did so weakly and only at very high concentrations. Uterine acid extracts also stimulated DNA synthesis. IGF-I stimulated at concentrations consistent with its acting through the IGF-I receptor; however, insulin stimulated at concentrations higher than expected for its acting through its receptor and this its action may be mediated through the IGF-I receptor. IGF-I was found in uterine tissue by radioimmunoassay (RIA). There was a 5- to 10-fold increase in IGF-I in the uteri from ovariectomized rats that had been treated with estradiol 24 h earlier. This is analogous to the increase in growth factor activity found previously in rat uterus after 24-h estradiol treatment (Beck, C.A. and Garner, C.W. (1989) Mol. Cell. Endocrinol. 63, 93-101). These data are consistent with the hypothesis that estradiol effects in the uterus are in part mediated through IGF-I.
Mol Cell Endocrinol 1992 Mar
PMID:Stimulation of DNA synthesis in rat uterine cells by growth factors and uterine extracts. 163 15

A murine fibroblast cell line (AKR-2B clone 84A) and an epithelial cell line (BALB/MK) were compared for their ability to bind different transforming growth factor-beta (TGF beta) species. The results of competitive binding assays indicated that the epithelial cells had a higher affinity for TGF beta than the fibroblasts. This difference may be the basis for the sensitivity of epithelial cells to much lower concentrations of TGF beta than fibroblasts. Affinity cross-linking studies showed that both cell types express the three cell surface TGF beta-binding molecules that have been previously described for a variety of cell types. The complexity of these cell surface binding proteins was further evaluated using all possible combinations of radiolabeled ligands in competition with each of the three unlabeled TGF beta species. Differences in the ability of specific TGF beta types to compete with radiolabeled TGF beta 2 for binding to the type I and II receptors were observed, with TGF beta 1 being more potent for epithelial cells, and TGF beta 2 being more potent for fibroblasts. In addition, a difference in the ability of different TGF beta species to compete the [125I]TGF beta 3 from epithelial cell surface receptors was apparent. TGF beta 2 was not able to compete with [125I]TGF beta 3 for binding to the type II receptor at any concentration tested, while TGF beta 1 and TGF beta 3 were about equally potent in competition for this receptor type. These differences in cell surface receptor binding of structurally and biologically similar molecules may reflect different functions for these molecules.
Mol Endocrinol 1991 Dec
PMID:Differential binding of transforming growth factor-beta 1, -beta 2, and -beta 3 by fibroblasts and epithelial cells measured by affinity cross-linking of cell surface receptors. 166 3

We have examined the histological and cytoskeletal changes in rat connective tissues induced by subcutaneous perfusion with cytokines. Granulocyte macrophage-colony stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-alpha), interleukin-1-alpha (IL-1-alpha), transforming growth factor-beta (TGF-beta) and platelet-derived growth factor (PDGF) produced a significant fibroblast accumulation, neovascular development and a weak to moderate leukocyte infiltration, while interleukin-2 (IL-2) and gamma-interferon (gamma-IFN) induced intense mononucleated leukocyte infiltration. Immunofluorescence staining showed that accumulated fibroblastic cells were positive for alpha-smooth muscle (SM) actin (but negative for the desmin and muscle myosin) only in GM-CSF-treated tissues. Electron microscopic examination established that a significant proportion of fibroblastic cell in GM-CSF-, IL-1-alpha- or TGF-beta-treated animals were typical myofibroblasts. Only in GM-CSF-treated animals did microfilament bundles of myofibroblasts contain alpha-SM actin, when examined by immuno electron microscopy. Our results suggest that locally applied cytokines induce the formation of distinct granulation tissues. In particular, GM-CSF stimulates alpha-SM actin synthesis in myofibroblasts, illustrating an unexpected extra-hematopoietic in vivo effect of this factor.
Virchows Arch B Cell Pathol Incl Mol Pathol 1991
PMID:Locally applied GM-CSF induces the accumulation of alpha-smooth muscle actin containing myofibroblasts. 167 12

A cDNA clone encoding a new member (designated GDF-1) of the transforming growth factor-beta (TGF beta) superfamily was isolated from a library prepared from day 8.5 mouse embryos. The nucleotide sequence of GDF-1 predicts a protein of 357 amino acids with a mol wt of 38,600. The sequence contains a pair of arginine residues at positions 236-237, which is likely to represent a site for proteolytic processing. The C-terminus following the presumed dibasic cleavage site shows significant homology with the known members of the TGF beta superfamily, matching the other family members at all of the invariant positions, including the seven cysteine residues with their characteristic spacing. GDF-1 is most homologous to Xenopus Vg-1 (52%), but is not likely to be the murine homolog of Vg-1. In vitro translation experiments were consistent with GDF-1 being a secreted glycoprotein. Genomic Southern analysis indicated that GDF-1 may be highly conserved across species. These results suggest that GDF-1 is most likely an extracellular factor mediating cell differentiation events during embryonic development.
Mol Endocrinol 1990 Jul
PMID:Identification of a novel member (GDF-1) of the transforming growth factor-beta superfamily. 170 86

The promoters for chicken transforming growth factor-beta 2 (TGF-beta 2) and TGF-beta 3 were cloned and sequenced to study the regulation of these genes. The promoters are GC-rich and lie within CpG islands. Several putative DNA regulatory sequence motifs were identified in the 5'-flanking regions, including matches to particular recognition sequences for several nuclear factors found in other genes. A comparison of chicken and human TGF-beta 2 promoters revealed a 111 bp conserved sequence surrounding the major transcription start site. Two regions of sequence homology were detected in the 5'-flanking regions of chicken and human TGF-beta 3 genes: an 86 bp sequence surrounding the major transcription start and a 156 bp sequence in the 5'-untranslated region. No DNA sequence homology was detected between TGF-beta 1, -beta 2 or -beta 3 promoters. The conserved region near the major transcription start sites in both the TGF-beta 2 and TGF-beta 3 genes, however, does show some structural homology; both promoters contain short conserved sequences that resemble TATA box, cyclic AMP-responsive element and AP-2 sequence motifs, cis-acting elements we believe may be important for promoter activity.
J Mol Endocrinol 1991 Dec
PMID:Comparative analysis of human and chicken transforming growth factor-beta 2 and -beta 3 promoters. 184 Jun 16

Most cell types have receptors for transforming growth factor-beta (TGF-beta) and respond similarly to TGF-beta 1 and TGF-beta 2. We have demonstrated the presence of a single class of high-affinity receptors (approximately 10,000 sites/cell) for TGF-beta 1 (Kd = 23 pM) and TGF-beta 2 (Kd = 41 pM) on early-passage rat lung fibroblasts (RLF). Incubation with unlabeled TGF-beta 1 and TGF-beta 2 resulted in concentration-dependent inhibition of binding of 15 pM [125I]TGF-beta 1 (ED50, 20 and 28 pM, respectively) and [125I]TGF-beta 2 (ED50, 36 and 56 pM, respectively). TGF-beta receptors affinity-cross-linked with 100 pM [125I]TGF-beta 1 or [125I]TGF-beta 2 were subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis and exhibited labeled protein bands of 68, 88, and 286 kD. Densitometric analysis of the resulting autoradiograms showed that the different molecular weight TGF-beta binding proteins exhibited separate affinities for the two forms of TGF-beta. Both TGF-beta 1 and TGF-beta 2 altered the morphology and cytoskeleton of RLF in a similar manner, but TGF-beta 1 was more potent than TGF-beta 2 in the inhibition of RLF growth and colony formation, with 50% inhibition by 0.12 pM TGF-beta 1 and 4.4 pM TGF-beta 2. Different affinities for the TGF-beta s may indicate selectivity among the receptor subtypes with regard to the biologic responsiveness of RLF to TGF-beta s. We believe this to be the first demonstration of biologically responsive TGF-beta receptors with different affinities for TGF-beta 1 and TGF-beta 2 on cells derived from normal, nonimmortal RLF. In establishing the basic mechanisms of pulmonary fibrosis, it will be essential to understand the biology and biochemistry of the receptors that may control cell division and production of extracellular matrix components by fibroblasts.
Am J Respir Cell Mol Biol 1991 May
PMID:Receptors for transforming growth factor-beta (TGF-beta) on rat lung fibroblasts have higher affinity for TGF-beta 1 than for TGF-beta 2. 185 Jun 5

The ontogeny of parathyroid hormone (PTH) and PTH-related protein (PTHrP) gene expression was studied by hybridization histochemistry in the rat at various stages between implantation and full term. PTHrP mRNA was demonstrable in the early postimplantation trophoblastic giant cells but disappeared from this site before 13.5 days. Localized gene expression, detectable by the in-situ technique, began between 12.5 and 15.5 days in embryonic tissues. The distribution of gene expression suggests that PTHrP may be concerned with the process of implantation. Its widespread, yet clearly localized, distribution in embryonic and fetal tissues is consistent with a paracrine or autocrine function which may relate to the transforming growth factor-beta family of growth factors. PTH expression occurred solely in the parathyroid and was detectable in the fetal parathyroid at 13.5 days of gestation.
J Mol Endocrinol 1991 Jun
PMID:Expression of parathyroid hormone-related protein mRNA in the rat before birth: demonstration by hybridization histochemistry. 188 89

Human T-cell lymphotropic virus type I (HTLV-I) has been associated with an adult form of T-cell leukemia as well as tropical spastic paraparesis, a neurodegenerative disease. Adult T-cell leukemia patients express high levels of the type 1 isoform of transforming growth factor-beta (TGF-beta 1), which is mediated by the effects of the HTLV-I Tax transactivator protein on the TGF-beta 1 promoter. To understand further the regulation of TGF-beta 1 expression by Tax, we examined its expression in transgenic mice carrying the HTLV-I tax gene. We show that tumors from these mice and other tissues, such as submaxillary glands and skeletal muscle, which express high levels of tax mRNA selectively express high levels of TGF-beta 1 mRNA and protein. Moreover, TGF-beta 1 significantly stimulated the incorporation of tritiated thymidine into one of three cell lines derived from neurofibromas of tax-transgenic mice, which suggests that the excessive production of TGF-beta 1 may play a role in tumorigenesis and that these mice may serve as a useful model for studying the biological effects of TGF-beta in vivo.
Mol Cell Biol 1991 Oct
PMID:Overexpression of transforming growth factor-beta in transgenic mice carrying the human T-cell lymphotropic virus type I tax gene. 192 42


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>