TGF-beta1 Gene Expression Research Articles

Coordinate gene expression during neonatal rat heart development. A possible role for the myocyte in extracellular matrix biogenesis and capillary angiogenesis.

Neonatal heart development is a period of active extracellular matrix deposition and capillary angiogenesis which follows the cessation of ventricular myocyte proliferation. The aim was to determine whether coordinate expression of growth factors by the ventricular myocyte could function to inhibit myocyte proliferation directly as well as indirectly by paracrine stimulation of non-myocyte extracellular matrix deposition and capillary angiogenesis. Immunohistochemistry and northern blot hybridisations were performed on ventricular samples from fetal to mature animals of the spontaneously hypertensive (SHR) and normotensive control Wistar Kyoto (WKY) strains. Ventricular expression of types I, III, and IV collagen genes reached their "maximum" within the first 2-3 postnatal weeks and then rapidly declined. Expression of TGF beta 3 and SPARC were found to precede and accompany the changes in extracellular matrix gene expression during this same developmental period. TGF beta 3 was immunolocalised to fetal cardiomyocytes with very limited expression in neonatal/adult non-myocytes. Associated with the neonatal expression of TGF beta variants, transcripts for the type 2 IGF receptor gradually declined over the first three postnatal weeks. Myocyte TGF beta gene expression, latent TGF beta release, and paracrine mechanisms of action could be facilitated by residual type 2 IGF receptor expression to help mediate stimulation of non-myocyte extracellular matrix synthesis and deposition. Expression of select growth factors, growth factor receptors, and components of the extracellular matrix appear to be highly coordinated during ventricular remodelling which occurs during neonatal heart development. A paradigm is presented which integrates the expression patterns of various myocyte derived stimuli and their postulated impact on formation of the structural components of the neonatal heart by modulation of myocyte and non-myocyte cell types.

In situ hybridization analysis of cytokine, proto-oncogene and tumour suppressor gene expression in psoriasis

The purpose of this study was to investigate and to compare, by in situ hybridization, gene expression of IL-1 beta, IL-8, TGF-beta 1, TGF-beta 2, TGF-beta 3, TGF-alpha, p53 and c-myc in lesions and in non-involved skin of patients with psoriasis. All lesional skin biopsies showed overexpression of IL-1 beta, IL-8 TGF-alpha mRNAs. IL-1 beta hybridization signals were strong in a small number of cells localized predominantly in the dermal papillae and in the suprapapillary epidermis. Overexpression of TGF-alpha was observed in all suprabasal keratinocytes, whereas strongly elevated IL-8 mRNA expression was found to be restricted to clusters of suprabasal keratinocytes. TGF-beta 3, p53 and c-myc transcripts were clearly detected in the epidermis of all biopsies, although expression levels were comparable in lesional and non-lesional skin.

TGF beta and HIV infection.

TGF beta is a cytokine which is involved with the regulation of different aspects of host defense responses to injury. Overexpression of TGF beta can lead to the conversion of its protective functions to pathogenetic manifestations. TGF beta is a potent factor in promoting anabolic aspects in connective tissue metabolism, and uncontrolled production of TGF beta has been associated with the development of fibrosis. With respect to its effects on immune and inflammatory responses, TGF beta is an important endogenous immunosuppressive factor which physiologically may protect the organism from tissue damage caused by chronic activation of leukocytes. As a result of overproduction in HIV infection, this function of TGF beta can contribute to noncytopathic mechanisms of immunodeficiency. TGF beta is involved with several aspects of HIV disease and promotes virus replication and spreading through multiple distinct mechanisms. It directly stimulates virus replication in infected monocytes and peripheral blood mononuclear cells under certain in vitro conditions. It may stimulate the production of other cytokines that enhance virus replication and it may be the mediator of other HIV-stimulating agents such as cocaine. It enhances recruitment of mononuclear phagocytes as cells susceptible to virus infection. Through its profound and broad inhibitory effects on different antiviral defense mechanisms, it facilitates more rapid progression of virus infection and increases susceptibility to opportunistic infections and malignancies. Although these findings are largely based on in vitro systems, the demonstration of TGF beta overexpression in HIV-infected patients supports the notion that this cytokine is an important pathogenetic mediator in HIV infection and its associated diseases. Therapeutic strategies to interfere with these functions of TGF beta are the development of TGF beta-neutralizing antibodies and soluble TGF beta-binding proteins and receptors as well as approaches directed at reducing TGF beta gene expression.

Cholesterol, macrophages, and gene expression of TGF-beta 1 and fibronectin during nephrosis.

Hypercholesterolemia aggravates experimental progressive glomerular injury. Evidence suggests the infiltrating glomerular macrophage (M phi) is a potential effector mechanism for the noxious effects of hypercholesterolemia. Because transforming growth factor (TGF)-beta 1 is secreted by activated M phi s and also stimulates fibronectin production by glomerular cells, we evaluated the kinetics of gene expression for these moieties in glomeruli isolated from nephrotic rats at 3, 7, 11, and 42 days after the delivery of puromycin aminonucleoside (PA). We also assessed whether cholesterol feeding, which raises the glomerular M phi number, alters the glomerular mRNA levels for TGF-beta 1 and fibronectin. Glomerular mRNA levels for TGF-beta 1 and fibronectin in nephrotic rats exhibited a biphasic temporal pattern, decreasing significantly below control at 3 and 7 days after PA but increasing significantly at 11 and 42 days after PA. The upregulated gene expression for TGF-beta 1 and fibronectin at 11 days after PA temporally corresponded to the phase of mesangial M phi infiltration in this model. Cholesterol feeding to both normal and nephrotic rats significantly increased glomerular TGF-beta 1 and fibronectin mRNA levels at 11 days after PA. Immunohistochemical labeling for M phi s and intracellular TGF-beta 1 demonstrated both mesangial and cortical interstitial localization with the TGF-beta1-positive cells possessing M phi nuclear morphology. These findings identify a novel interaction between hypercholesterolemia, augmented glomerular M phi accumulation, and upregulated glomerular TGF-beta 1 and fibronectin gene expression. These perturbations within the acutely injured glomerulus constitute an early pathobiological determinant for the later development of mesangial matrix expansion and glomerulosclerosis.

Reduced expression of TGF β is associated with advanced disease in transitional cell carcinoma

The gene structure and expression of the related peptide regulatory factors TGF beta 1 and TGF beta 2 were studied in a panel of seven urothelial carcinoma cell lines and 40 transitional cell carcinomas. The latter comprised 15 grade 1, 18 grade 2 and 5 grade 3 tumours and two cases of carcinoma in situ. Control tissues included ten matched 'field' biopsies and 17 other biopsies including 11 biopsies of macroscopically normal urothelium, two of which were from patients with no history of bladder cancer. No amplification of rearrangements of either TGF beta 1 or TGF beta 2 were detected in any sample. A complex pattern of expression or the two genes was found in the urothelial cell lines. High, but variable levels of the 2.5 kb TGF beta 1 transcript were detected and lower and more variable levels of the three (4.1 kb, 5.1 kb and 6.5 kb) transcripts of TGF beta 2 were detected. Although those cell lines expressing most TGF beta 1 tended to express less TGF beta 2 transcript there was no clear-cut relationship. In comparison, no TGF beta 2 transcript was identified in any primary transitional cell carcinoma or control tissue. Markedly reduced or undetectable levels of TGF beta 1 transcript were detected in 4/15 (26%) grade 1, 5/18 (28%) grade 2 and 3/5 (60%) grade 3 tumours. There was no clear relationship to tumour stage, lymphocytic infiltration or stromal content of the tumours. Clinical review one year after the 2 year period of tumour collection showed that 6/9 (66%) of patients with tumours with reduced levels of transcript had died or had disease which was not controllable by local resection and 3/9 (33%) had developed tumour re-occurrences. In comparison, in the group with normal levels of expression of TGF beta 1, 3/18 (17%) had disease which was not controllable by local means, 9/18 (50%) had tumour re-occurrence and 6/18 (33%) had no evidence of disease. The association of reduced expression of TGF beta 1 and advanced disease was statistically significant P < 0.02 (Fisher's test). Although the sample size is small, we suggest that the loss of expression of TGF beta 1 may be a potential marker of progressive disease or prognosis in transitional cell carcinoma and warrants further study.

Low-protein diet attenuates increased gene expression of platelet-derived growth factor and transforming growth factor-beta in experimental glomerular sclerosis.

The present study was designed to assess whether platelet-derived growth factor (PDGF)-A and -B chain and transforming growth factor-beta (TGF-beta) mRNA expression in glomeruli are affected by a low-protein (6%) diet during the course of focal glomerulosclerosis (FGS). Puromycin aminonucleoside (PAN) was injected intraperitoneally in rats, and the right kidney was removed on day 22. The nephrotic rats received successive intraperitoneal injections of PAN on days 27, 34, and 41. Control rats were subjected to a sham operation on day 22. The PAN-injected rats were divided into two groups. Group 1 rats were fed a standard diet containing 22% protein, whereas group 2 rats were fed a low-protein diet containing 6% protein, starting on the same day as the first PAN injection. Rats were killed on days 0, 48, 60, and 80 after the initial PAN injection. The percentage of sclerotic glomeruli in group 1 rats increased markedly with time, reaching 73% on day 80. The PDGF-A and -B chain and TGF-beta mRNA levels increased significantly as glomerulosclerosis progressed. A positive correlation was noted between the PDGF and TGF-beta mRNA levels and the incidence of glomerular sclerosis. The low-protein diet reduced the prevalence of glomerular sclerosis (10% on day 80) and attenuated the abnormally high expression of PDGF-A and -B chain and TGF-beta genes in FGS glomeruli. These findings suggest that PDGF and TGF contribute to glomerulosclerosis and that a low-protein diet attenuates markedly the increased glomerular expression of the PDGF and TGF-beta genes in glomerular sclerosis.

Differential expression of TGF beta isoforms by human articular chondrocytes in response to growth factors.

Transforming growth factor beta (TGF beta) is a family of important regulators of chondrocyte growth and differentiation. Although TGF beta has been detected in cartilage, the TGF beta isoforms expressed by chondrocytes and their regulation by growth factors are unknown. This study shows that human articular chondrocytes release TGF beta activity. Chondrocyte conditioned media contains active TGF beta and larger quantities in latent form. By neutralization with specific antibodies it is shown that all three isoforms (TGF beta 1, TGF beta 2, and TGF beta 3) are secreted by chondrocytes. Analysis of the inducers of TGF beta gene expression demonstrates complex regulation of TGF beta production by growth factors. Basic fibroblast growth factor (bFGF) stimulates the release of TGF beta activity but has no effect on steady state TGF beta mRNA levels while platelet-derived growth factor (PDGF) upregulates TGF beta 1 and TGF beta 3 mRNAs with a corresponding increase in protein secretion. The three TGF beta isoforms themselves differentially affect gene expression. While TGF beta 1 and TGF beta 2 show autoinduction, TGF beta 3 upregulates TGF beta 1 but does not affect TGF beta 2 mRNA levels. These results demonstrate that human articular chondrocytes produce all three TGF beta isoforms. Induction of TGF beta expression is differentially regulated by various growth factors and occurs at the mRNA level and/or posttranscriptionally. Chondrocyte expression and the differential regulation of TGF beta 1, TGF beta 2, and TGF beta 3 by growth factors suggest that all three isoforms of TGF beta are part of the network of cartilage regulatory factors.

B-cell chronic lymphocytic leukaemia cells express and release transforming growth factor-beta.

Transforming growth factor-beta (TGF-beta) has been described as a potent inhibitor of various cell types, among others of primitive haematopoietic progenitors in vitro, and as a negative autocrine regulator of normal B lymphocyte growth and differentiation. In the present study we investigated TGF-beta gene expression in peripheral blood mononuclear cells (PBMC) and in B cells from patients with B-cell chronic lymphocytic leukaemia (B-CLL) and from normal controls. Monocyte depleted B-CLL cells expressed constitutively mRNA for TGF-beta 1 and secreted low amounts of TGF-beta activity into the culture medium. Stimulation of cells by phorbol ester noticeably enhanced mRNA levels as well as protein secretion in most cases. TGF-beta activity was of the same magnitude as in normal controls. We next analysed TGF-beta in highly enriched B lymphocytes from B-CLL (95-100% CD19+), and found that TGF-beta secretion was up to 3 times higher than in the original PBMC population. It is discussed that B-CLL cells might escape from negative regulation by TGF-beta and, on the other hand, inhibit normal haematopoietic cell proliferation and thereby achieve a growth advantage in the haematopoietic tissues.

Modulation of Transforming Growth Factor-βProduction in Normal Human Osteoblast-Like Cells by 17β-Estradiol and Parathyroid Hormone

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.

Gene expression of cytokines suppressing hematopoietic progenitor cells in lymphoid malignancies

The expression of cytokine genes for tumor necrosis factor alpha (TNF alpha), lymphotoxin and transforming growth factor beta (TGF beta), all of which are known to suppress normal hematopoiesis, was investigated in 32 patients with lymphoid malignancies using Northern blot analysis. Messenger RNA (mRNA) for TNF alpha, lymphotoxin and TGF beta was detected in 9 cases, 2 cases and 7 cases, respectively. When the relationship between cytokine gene expression and surface phenotype was analyzed, the expression of CD19 correlated significantly with expression of the TNF alpha gene (P less than 0.05). This suggests that B cell malignancies are likely to produce TNF alpha. When the hematological parameters of patients expressing and not expressing the gene were compared, the expression of TNF alpha mRNA was found to correlate with more profound anemia in acute lymphoblastic leukemia (P less than 0.05). Both granulocyte and platelet counts were lower in patients expressing TNF alpha mRNA; however, the decreases were not significant. Neither lymphotoxin nor TGF beta gene expression correlated significantly with any hematological parameter.

Increases in transforming growth factor‐β mRNA in hippocampus during response to entorhinal cortex lesions in intact and adrenalectomized rats

Transforming growth factor-beta mRNA was detected with a rat TGF-beta 1 coding sequence probe as a 2.5 kb band by RNA blot hybridization of total RNA from the adult male rat hippocampus. Following electrolytic lesions of the entorhinal cortex that cause hippocampal deafferentation and synaptic remodeling, TGF-beta mRNA increases 5-fold in ipsilateral hippocampus when compared with intact controls. This increase was independent of prior adrenalectomy or corticosterone-replacement. These data demonstrate that TGF-beta gene expression increases in response to hippocampal deafferentation.

Regulation of TGFβ gene expression in rat liver intoxicated with carbon tetrachloride

Transforming growth factor beta (TGF beta) has been implicated as having a central role in the postinflammatory tissue regeneration and fibrosis. To test its potential involvement in events that follow hepatotoxin-mediated liver regeneration and fibrosis, we quantitated changes in the steady-state levels of TGF beta mRNA in parenchymal and nonparenchymal cells at various times after an acute treatment with CCl4, and also compared TGF beta gene expression in these two cell types from livers subjected to chronic CCl4 treatment. The parenchymal and nonparenchymal cells from normal liver contained undetectable amounts of TGF beta mRNA. In contrast, we could readily detect TGF beta specific transcripts in both the parenchymal and nonparenchymal cells after acute injury. Nonparenchymal cells from acutely injured liver contained fivefold greater amounts of TGF beta mRNA, which peaked at 48 h and declined thereafter. In chronically treated rat livers (1, 2, 3, and 7 wk after the initiation of CCl4 treatment), increased expression of TGF beta mRNA was found only in nonparenchymal cells obtained after 2-3 wk of treatment. Strikingly large elevations in the steady-state levels of beta-actin mRNA in CCl4-treated liver were also observed, which may be related to the known regenerative processes associated with acute liver toxicity. Changing dynamics of TGF beta gene expression, therefore, appear to be an important attribute of regenerating liver after acute or chronic CCl4 toxicity.

Coordinate regulation of transforming growth factor beta gene expression and cell proliferation in hamster lungs undergoing bleomycin-induced pulmonary fibrosis.

The number of mesenchymal cells, as well as their ability to synthesize extracellular matrix (ECM) components, greatly increase in the interstitium of fibrotic lungs. We have previously shown that the transcription of type I procollagen and fibronectin genes in the lungs is preferentially elevated during the early stages of bleomycin-induced pulmonary fibrosis (Raghow, R., S. Lurie, J. M. Seyer, and A. H. Kang. 1985, J. Clin. Invest. 76:1734-1739. Since a cytokine-like transforming growth factor beta (TGF beta) that is capable of enhancing mesenchymal cell proliferation and ECM synthesis could be potentially involved in this process, we investigated the temporal relationship between the regulation of TGF beta gene transcription and cellular proliferation in the bleomycin-treated hamster lungs. We observed a transient 5-7-fold increase in the accumulation of TGF beta transcripts, a concomitant 3-4-fold elevation in the cellular proliferation, and 8-10-fold stimulation of DNA synthesis in these lungs; all three parameters peaked around day 10 after bleomycin administration. Based on these results, we conclude that regulation of TGF beta gene expression may contribute significantly to the early events that lead to bleomycin-induced pulmonary fibrosis.

Fibroblast growth factor enhances type beta 1 transforming growth factor gene expression in osteoblast-like cells.

Fibroblast growth factor (FGF) and type beta transforming growth factor (TGF beta) are potent modulators of proliferation and differentiation in many types of cells. TGF beta acts in an autocrine manner, and the regulation of TGF beta gene expression is one of the crucial events in the control of cellular functions. This study examines FGF regulation of TGF beta 1 gene expression in osteoblast-like cells. Bovine basic FGF (bFGF) increased the steady-state level of 2.5-kb TGF beta 1 mRNA two- to threefold in rat osteosarcoma (ROS17/2.8) cells in a dose-dependent manner, starting at 0.1 ng/ml. The increase of the message was detectable within 3 h after the addition of bFGF, peaked at 6 h, and lasted at least up to 48 h. This effect was blocked by a protein kinase inhibitor, K252a, indicating the involvement of phosphorylation. bFGF increased the rate of TGF beta 1 gene transcription estimated by nuclear run-on assay, while the stability of TGF beta 1 mRNA was not altered. bFGF increased the TGF beta activity in the conditioned media, estimated by DNA synthesis inhibition assay using mink lung epithelial (CCL-64) cells. Parathyroid hormone reduced the abundance of TGF beta 1 mRNA in ROsS17/2.8 cells and opposed the bFGF effect on TGF beta 1 mRNA. bFGF also increased the steady-state level of TGF beta 1 mRNA in mouse calvaria-derived MC3T3E1 and human osteosarcoma SaOS-2 cells. These findings indicate that FGF enhances the expression of TGF beta 1 gene in osteoblast-like cells and point to the tight relationship of the two growth factors involved in the control of cellular functions.

TGF beta gene transcription in normal and neoplastic liver growth.

TGF beta is a potent, nontoxic inhibitor of mitogen-induced DNA synthesis in primary cultures of adult rat hepatocytes. Using a cDNA probe, we investigated TGF beta gene expression in quiescent, regenerating, and neoplastic liver, and several hepatoma lines by Northern gel analysis. We found that regenerating liver had increased TGF beta gene transcripts beginning at about 8 h, with a broad peak of 48-120 h and return to normal after 9 days. Separation of the regenerating liver into its constituent cell types, followed by RNA extraction and reprobing, revealed that increased TGF beta gene transcripts were confined to the enriched endothelial-cell population and not the hepatocytes. Increased hepatic TGF beta expression was also found in fetal liver and in rats immediately after birth. Elevated TGF beta mRNA levels were also found in primary cultures of oval cells and an established bile ductular cell line, as well as in carcinogen-altered liver epithelial cell lines. Transcripts were undetectable in normal human liver but were abundant in the human hepatoma lines Hep G2, Hep 3B, PLC/PRF/5, and SK-Hep-1. Elevated levels were also found in the normal rat liver-derived lines BRL-3A and clone 9 and the H4IIE rat hepatoma, but not in the HTC, MH1C1, and MH7777 rat hepatomas. The hepatocarcinogen diethylnitrosamine induced high transcript levels after single injections in a time- and dose-dependent manner. These results suggest that the liver may be a paracrine organ with respect to TGF beta gene expression, which can be induced by carcinogens and by growth stimulation.

Expression of TGF-Beta Gene in Adult T Cell Leukemia

Peripheral mononuclear cells from adult T cell leukemia (ATL) patients were analyzed in comparison with other types of leukemia cells, for the expression of transforming growth factor-beta (TGF-beta) mRNA, for the presence of TGF-beta activity (colony stimulating activity for normal rat kidney fibroblasts [NRK]) in conditioned medium and for their susceptibility to exogenous TGF-beta. Highly elevated TGF-beta mRNA levels were observed in all five ATL cell samples tested; however, in three acute myelogenous leukemia (AML) samples, in one acute lymphatic leukemia (ALL), and one chronic myelogenous leukemia (CML), TGF-beta expression was relatively lower. In normal peripheral mononuclear cells TGF-beta mRNA was weakly detectable. Colony stimulating activity for NRK found in the conditioned medium from ATL cells as well as other leukemia cells correlated well with the levels of TGF-beta mRNA expression. In all three ATL samples tested, stimulation of 3H-thymidine uptake by purified TGF-beta from platelets was apparent. These results suggest that ATL cells are secreting active TGF-beta in a relatively high amount, as compared with other leukemia cells, and may proliferate in response to the factor via an autocrine manner. Furthermore, considering that TGF-beta stimulates bone resorption, we can speculate that the relatively high amount of TGF-beta in ATL cells contributes to the hypercalcemia frequently seen in ATL patients.

Expression of TGF-beta gene in adult T cell leukemia

Peripheral mononuclear cells from adult T cell leukemia (ATL) patients were analyzed in comparison with other types of leukemia cells, for the expression of transforming growth factor-beta (TGF-beta) mRNA, for the presence of TGF-beta activity (colony stimulating activity for normal rat kidney fibroblasts [NRK]) in conditioned medium and for their susceptibility to exogenous TGF-beta. Highly elevated TGF-beta mRNA levels were observed in all five ATL cell samples tested; however, in three acute myelogenous leukemia (AML) samples, in one acute lymphatic leukemia (ALL), and one chronic myelogenous leukemia (CML), TGF-beta expression was relatively lower. In normal peripheral mononuclear cells TGF-beta mRNA was weakly detectable. Colony stimulating activity for NRK found in the conditioned medium from ATL cells as well as other leukemia cells correlated well with the levels of TGF-beta mRNA expression. In all three ATL samples tested, stimulation of 3H- thymidine uptake by purified TGF-beta from platelets was apparent. These results suggest that ATL cells are secreting active TGF-beta in a relatively high amount, as compared with other leukemia cells, and may proliferate in response to the factor via an autocrine manner. Furthermore, considering that TGF-beta stimulates bone resorption, we can speculate that the relatively high amount of TGF-beta in ATL cells contributes to the hypercalcemia frequently seen in ATL patients.

An early comment on isostatic compensation

The inflammatory process in the brain requires bidirectional interaction of the immune and nervous systems. Evidently, astrocytic glial cells play an important role in facilitating this communication by releasing immunomodulators and cytokines. Expression of transforming growth factor beta-1 (TGF beta-1), a potent inhibitor of T cell function and glial cell proliferation, is highly regulated in T cells and is believed to be an important component in the molecular interaction between the immune and nervous systems. Comparative analysis of TGF beta-1 gene expression in human T and glial cells by Northern hybridization and S1 nuclease protection assay showed that dexamethasone (DM) caused a significant decrease in the basal and PMA-induced levels of TGF beta-1 mRNA in glial cells but not in T cells. This reduction correlated with a lower level of TGF beta-1 protein production. Transient transfection assay using deletion constructs of the 59 TGF beta-1 gene promoter-containing sequences between -453 and +11 bp identified a region spanning -160 to -60 bp as a potential sequence responsive to regulation by DM in T cells, whereas in glial cells, the overall transcriptional activity of the 59 TGF beta-1 promoter was reduced after DM treatment, but promoter activity within each construct remained constant in response to DM. Thus, a DM-responsive region could not be identified within the TGF beta-1 promoter in glial cells. These findings suggest that TGF beta-1 gene expression is differentially regulated by distinct regulatory elements in T and glial cells, and that extracellular stimulators, including glucocorticoids, can utilize the TGF beta-1-regulatory pathway to affect the functions of neural and immune cells.