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Query: UMLS:C1852438 (CCL)
 1,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using a transforming growth factor-beta (TGF beta)-sensitive cell line, Mv1Lu (or CCL 64), we demonstrated that trophoblasts predominantly produced a latent form of TGF beta. After converting latent TGF beta to active TGF beta in vitro by acid (pH 2.5), alkali (pH 10.0), or heat (90 C; 10 min) treatment, addition of rabbit anti-TGF beta 1 antiserum resulted in the elimination of TGF beta activity, thus suggesting that trophoblasts produced at least a certain amount of latent TGF beta 1. To investigate the role of TGF beta 1 in placental hormonogenesis, we first studied the effect of recombinant (r) TGF beta 1 on the production of interleukin-6 (IL-6) and hCG by trophoblasts. rTGF beta 1 exerted no inhibitory activity on IL-6 and hCG production. The effect of rTGF beta 1 on cytokine-induced IL-6 and hCG release was then examined. While rTGF beta 1 failed to inhibit basal hCG secretion, it did inhibit recombinant tumor necrosis factor-alpha (rTNF alpha)-induced IL-6 release as well as rTNF alpha- and rIL-6-induced hCG release in a dose-dependent manner. However, rIL-1 alpha-induced IL-6 and hCG release was remarkably sensitive to rTGF beta 1-mediated suppression. In contrast, GnRH-induced hCG release, the response of which is independent of the IL-6 and IL-6 receptor system in trophoblasts, was completely resistant to rTGF beta 1. Thus, trophoblast-derived TGF beta 1 is an important regulatory molecule of cytokine-dependent, but not cytokine-independent, hCG release, possibly by converting latent TGF beta to active TGF beta at the local site of trophoblasts.
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PMID:Trophoblast-derived transforming growth factor-beta 1 suppresses cytokine-induced, but not gonadotropin-releasing hormone-induced, release of human chorionic gonadotropin by normal human trophoblasts. 172 23

Although our laboratory has reported that normal human osteoblast-like (hOB) cells contain estrogen receptors, we have failed to find major effects of 17 beta-estradiol (E2) on modulation of proliferation of bone matrix protein production by hOB cells. Because the major effect of E2 in vivo is to decrease bone resorption and because transforming growth factor-beta (TGF-beta) has been reported to decrease osteoclast-mediated bone resorption, we have tested the hypothesis that the effect of E2 on osteoclast activity is, at least in part, indirectly mediated by enhancing production of TGF-beta by osteoblasts. We therefore have extended our studies to examine possible TGF-beta gene expression including the modulation of the release of TGF-beta by E2 in near homogenous populations of hOB cells. TGF-beta protein production was measured using growth inhibition of CCL-64 cells and verified by blocking effects with anti-TGF-beta antibodies. TGF-beta 1 messenger RNA (mRNA) steady state levels were assessed by northern blot analysis and quantitated by densitometric measurement using 18S ribosomal RNA as a reference. There was an E2 dose-dependent increase in TGF-beta protein production within 24 h of challenge with E2. Northern blots from these cells demonstrated a dose-dependent increase in steady state mRNA levels of TGF-beta 1 within 6 h of treatment. PTH was also a potent stimulator of TGF-beta protein and message levels in a dose-dependent manner. Interestingly, coincubation of equimolar concentrations of E2 and PTH (10(-8) M) abrogated the stimulation of TGF-beta 1 mRNA and protein. Decreasing the relative concentration of PTH in this coincubation with E2 increased TGF-beta 1 mRNA and protein levels. These data support the fact that E2 modulates TGF-beta production in osteoblasts. In this manner TGF-beta may mediate E2 inhibition of osteoclast activity.
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PMID:Modulation of transforming growth factor-beta production in normal human osteoblast-like cells by 17 beta-estradiol and parathyroid hormone. 195 7

The anterior chamber of the eye is an immunologically privileged site. Over the past 15 years, numerous laboratories documented that the privileged status of this unique site is mediated by multifactorial immunoregulatory processes. Among the participating factors is the aqueous humor that circulates in the anterior chamber and is in contact with most of the tissues in the anterior segment of the eye. Recently, it was found that normal aqueous humor is a powerful inhibitor of antigen-driven T lymphocyte activation, but it spares other important functional properties of T cells. The spectrum of immune inhibitory properties resembles some of the activities of transforming growth factor-beta (TGF-beta), a polypeptide cytokine. Because of this similarity, the authors tried to determine if TGF-beta is present in aqueous humor and whether this cytokine could account for the lymphocyte inhibitory activity of this biologic fluid. They found TGF-beta in aqueous humor by dot-blot analysis. Using the CCL-64 mink lung epithelial cell bioassay for this compound, TGF-beta bioactivity was shown in aqueous humor from several different species, including human. In rabbit and human aqueous humor, most of the biologic activity was due to TGF-beta 2 (80-90%). Dose-response curves generated by using purified porcine TGF-beta showed that aqueous humor contained sufficient concentrations of TGF-beta to account for the observed inhibition in several assays for T cell activation and proliferation. Partial purification of the lymphocyte inhibitor in rabbit aqueous humor by size exclusion in high-performance liquid chromatography demonstrated that several lymphocyte inhibitory fractions contained TGF-beta bioactivity. Finally, neutralizing antisera to TGF-beta 2 were able to reverse most of the lymphocyte inhibitory activity of aqueous humor. It was concluded that TGF-beta was present in high concentration in normal aqueous humor and that this cytokine contributed to the immunosuppressive properties of aqueous humor.
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PMID:Identification of transforming growth factor-beta as an immunosuppressive factor in aqueous humor. 207 34

To examine the mechanisms by which transforming growth factors (TGFs) regulate the proliferation of eukaryotic cells, five cell lines, from different species and tissues, were treated with three agents that inhibit DNA synthesis and proliferation: BSC-1 cell-derived growth inhibitor (GI/TGF-beta), platelet-derived transforming growth factor-beta (TGF-beta), and 12-O-tetradecanoylphorbol-13-acetate. The cell lines tested were mink lung CCL 64 epithelial cells, Maloney sarcoma virus-transformed CCL 64.1, monkey kidney BSC-1 epithelial cells, human epidermoid A431 cells, and mouse embryo AKR-2B (clone 84A) cells. All cell lines responded to one or more of these agents by synthesizing and secreting a 48 to 51-kDa protein (IIP48). The TGF-beta s and 12-O-tetradecanoylphorbol-13-acetate had little or no effect on the incorporation of [35S] methionine into other secreted proteins or on the pattern of [35S]methionine-labeled intracellular proteins analyzed by one-dimensional, sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The maximum increase in induction of IIP48 varied from 2-fold to greater than 800-fold compared with the controls and occurred within 6 h of adding GI/TGF-beta to CCL 64 cells. Actinomycin D, alpha-amanitin, or 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole selectively decreased both the control and induced levels of IIP48 even after as little as 6 h of incubation. Thus, it appears that IIP48 mRNA turns over rapidly. Induction of IIP48 was dissociated from the inhibition of DNA synthesis by GI/TGF-beta. However, we found that epidermal growth factor and GI/TGF-beta act synergistically to increase the secreted level of IIP48. Others have shown that epidermal growth factor and TGF-beta act synergistically to stimulate growth of cells in agar. IIP48 from CCL 64, BSC-1, and AKR-2B cells is specifically immunoprecipitated by antibody to bovine plasminogen activator inhibitor. We found previously that TGF-beta also inhibits the production of major excreted protein, a thiol protease. It is proposed that TGF-beta is able to promote anchorage-independent growth of untransformed cells because of its ability to inhibit the production of secreted proteases and to increase the production of protease inhibitors.
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PMID:Specific induction of secreted proteins by transforming growth factor-beta and 12-O-tetradecanoylphorbol-13-acetate. Relationship with an inhibitor of plasminogen activator. 243 80

Our previous study indicated that polypeptides isolated from acid/ethanol extracts of solid tumors of a cloned F9-3 embryonal carcinoma cells by Bio-Gel P60 column chromatography were found to be able to stimulate anchorage independent growth of either NIH 3T3 cells or NRK 49 F cells in soft agar. The major peak of active elute had a molecular weight of about 15 kDa as determined by SDS-polyacrylamide gel electrophoresis. In the present report we further isolated and purified the active compound corresponding to molecular weight of 15 kDa by gel filteration on Bio-Gel P10 column (Fig. 1) and then by high pressure liquid chromatography (Fig. 2). It was found that the purified 15 kDa molecules showed some properties similar to transforming growth factor-beta (TGF-beta): 1. Colony-stimulating activity in soft agar can be induced in NRK 49 F cells only in the presence of mouse epidermal growth factor (EGF) (Plate I); 2. Increase in relative uptake of 3H-thymidine in NRK 49 F cells occurred in the presence of EGF, but with the same amount of EGF, not much change in 3H-thymidine incorporation could be found with further increasing amounts of purified 15 kDa molecules (Fig. 3); 3. Like human blood platelets derived TGF-beta, inhibition effect on the growth of mink lung epithelial cells (CCL/64) can also be exhibited by purified 15 kDa molecules (Fig. 4). In addition, using ELISA procedure, we have also demonstrated that the 15 kDa molecules had immunological reactivity with the antibody raised against a synthetic oligopeptide identical to the N-terminal residues 1-29 of TGF-beta 1 from human blood platelets (Fig.5). Thus, the 15 kDa molecules isolated from mouse F9-3 embryonal carcinoma cells appeared to share some common antigenic determinants with human TGF-beta 1 molecule. These results taken together provide strong support for the existence of TGF-beta like growth factor in mouse embryonal carcinoma cells.
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PMID:[A transforming growth factor-beta like growth factor in mouse embryonal carcinoma cells]. 280 Aug 39

Immunosuppressants such as cyclosporine are considered to constrain cell growth by preventing the production of growth stimulatory cytokines (e.g., interleukin-2). The possibility exists, however, that CsA and other immunosuppressants might restrain cell growth by promoting the production of growth-inhibitory cytokines. We have explored herein the hypothesis that CsA stimulates the production of transforming growth factor-beta (TGF-beta), and restrains new DNA synthesis in mammalian cells via a TGF-beta-dependent mechanism. To investigate this new postulate independently of an IL-2-dependent mechanism, we utilized, as probes, two mammalian cell lines, distinguished by their sensitivity to growth inhibition by TGF-beta and resistance to IL-2: CCL-64 mink lung epithelial cells (CCL-64 cells) and A-549 human adenocarcinoma cells (A-549 cells). Our experimental approach revealed the following: (A) CsA and not cyclosporine H, an inactive analogue of CsA, mediates growth inhibition of TGF-beta-sensitive cells, CCL-64 cells, and A-549 cells; (B) CsA stimulates these mammalian cells to secrete TGF-beta; and (C) TGF-beta induced by CsA is biologically active in inducing cell growth inhibition (demonstrated by the reversal of CsA-associated inhibition with anti-TGF-beta monoclonal antibodies). Our observations suggest that CsA can regulate cell growth via a TGF-beta-dependent mechanism. Since the multifunctional cytokine TGF-beta can enhance extracellular matrix accumulation as well as augment endothelin production, our findings also advance a mechanism that links, via TGF-beta, the beneficial (immunosuppression) and the harmful (fibrosis, hypertension) consequences of CsA usage.
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PMID:Regulation of new DNA synthesis in mammalian cells by cyclosporine. Demonstration of a transforming growth factor beta-dependent mechanism of inhibition of cell growth. 811 45

The RRR-alpha-tocopheryl succinate form of vitamin E inhibits the proliferation of estrogen receptor-positive and estrogen receptor-negative human breast cancer cell lines in a dose-dependent manner in vitro. Analyses of cell-conditioned medium from RRR-alpha-tocopheryl succinate growth-inhibited cells revealed the presence of a potent antiproliferative activity. Characterization of the antiproliferative activity as transforming growth factor-beta (TGF-beta) was established by 1) growth inhibition of the TGF-beta-responsive Mv1Lu-CCL-64 mink lung and murine CTLL-2 cell lines, 2) combination of physical characteristics including heat stability, acid stability, and Bio-Gel P-60 column chromatography elution profile, and 3) neutralization of the antiproliferative activity in the conditioned media by antibodies specific for TGF-beta.
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PMID:RRR-alpha-tocopheryl succinate inhibits proliferation and enhances secretion of transforming growth factor-beta (TGF-beta) by human breast cancer cells. 834 72

Treatment of primary rat embryo hippocampal neuronal cultures with 10(-5) M beta-amyloid peptide fragment 25-35 (A beta P) for 24 h resulted in a 60% decrease in cell viability as determined by MTT incorporation. When these cells were treated with 0.1-10 ng/ml of either transforming growth factor-beta (TGF-beta) 1, 2 or 3 for 24 h before exposure to A beta P, there was a 2.9-, 1.9-, and 3.2-fold increase in cell survival, respectively, compared to cells treated with A beta P alone. The viability of cells treated with A beta P and 0.1-10 ng/ml TGF-beta was comparable to that of cells not treated with A beta P. The protective effects were less pronounced at lower TGF-beta concentrations. The protective effects of pretreatment with TGF-beta were less striking in mouse CCL-N-2a and human SK-N-SH neuroblastoma cell lines. When all cells were treated with TGF-beta for 24 h following a 24 h exposure to A beta P, there was a trend toward increased cell viability which was less significant than pretreatment with TGFs-beta. An isoform-specific TGF-beta SELISA showed that primary hippocampal neuronal cultures and the neuroblastoma cell lines secrete all 3 TGF-beta isoforms. Based on our results, we propose that the increased expression of TGF-beta observed in brains of patients with Alzheimer's disease may offer some degree of neuroprotection.
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PMID:Transforming growth factors-beta protect primary rat hippocampal neuronal cultures from degeneration induced by beta-amyloid peptide. 889 Dec 64

Our previous in vivo analyses have suggested that astrocytes play a key role in retinal vascularization by inducing endothelial cell differentiation. Here we demonstrate that medium conditioned by cultured rat brain astrocytes (ACM) contains factors, including transforming growth factor-beta (TGF-beta), that inhibit endothelial cell growth. Serum-free medium conditioned for 1-3 days was tested on exponentially growing bovine retinal microvascular endothelial, aortic endothelial, mink lung epithelial CCL-64, and Swiss mouse 3T3 fibroblast cells. The growth of all four cell types was inhibited in a dose- and time-dependent manner. CCL cells, which are used as a model for assaying TGF-beta activity, were more sensitive than the endothelial cells, suggesting that ACM contains TGF-beta. Moreover, acid treatment significantly increased the inhibitory activity of ACM, indicating that TGF-beta in ACM is predominantly in the latent form. Mouse fibroblasts, which are not affected by TGF-beta treatment under the same conditions, were also inhibited by ACM. This suggests that other inhibitory factors in addition to TGF-beta may be involved. Adsorption by an anti-TGF-beta polyclonal antibody column substantially reduced but did not eliminate the inhibitory activity of ACM for CCL and endothelial cells. Western blot analysis of ACM and proteins eluted from the affinity column revealed a 25 kDa band that co-migrates with TGF-beta. Comparative densitometry of the 25 kDa bands on Western blot indicated that the amount of TGF-beta in ACM is not sufficient to account for the total growth-inhibitory activity. These experiments demonstrate directly that rat brain astrocytes express TGF-beta. They also indicate that astrocytes may produce other growth-inhibitory factor(s) yet to be identified.
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PMID:Angiostatic role of astrocytes: suppression of vascular endothelial cell growth by TGF-beta and other inhibitory factor(s). 892 41

An increasing body of evidence indicates that the oocyte plays an active role in the control of ovarian follicle development in mammals. In the present study, we have examined the role of oocytes in regulating granulosa cell proliferation. Rat and bovine oocytes cocultured with rat granulosa cells stimulated granulosa cell DNA synthesis and DNA content in the cultures. FSH or cAMP further amplified this effect. Poor-quality oocytes showed a marked decrease in their stimulatory effect. Stimulation of DNA synthesis by bovine oocytes seems to be cell-type specific, since Swiss 3T3 fibroblasts and CCL-64 mink lung epithelial cells were not responsive, while primary cultures of rat and bovine granulosa cells and the bovine granulosa cell line BGC-1 showed significant responses. Oocyte-conditioned medium produced only a slight stimulation of rat granulosa cell DNA synthesis. However, the effect of oocyte coculture was dependent on the total incubation volume, suggesting that the growth promoting activity was mediated by a soluble factor. The stimulation elicited by bovine oocytes was evident even in the presence of maximally effective doses of transforming growth factor-beta or tumor necrosis factor-alpha, indicating that neither of these growth factors was responsible for this effect. In vitro maturation of bovine oocytes was associated with a marked decrease in the stimulatory activity. This decrease was partially prevented when maturation was blocked by addition of cycloheximide. Comparison of the developmental pattern of the secretion of the growth promoting activity with that of the cumulus expansion-enabling factor indicated that both activities can be dissociated. Our data suggest the existence of a very labile factor produced by the oocyte before completion of the first meiotic division that promotes granulosa cell proliferation.
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PMID:Growth promoting activity of oocytes on granulosa cells is decreased upon meiotic maturation. 957 24


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