scholarly journals Expression of mRNA for IL1 beta, IL6 and TGF beta 1 in developing human bone and cartilage.

1994 ◽  
Vol 42 (6) ◽  
pp. 733-744 ◽  
Author(s):  
R A Dodds ◽  
K Merry ◽  
A Littlewood ◽  
M Gowen
Keyword(s):  
Mrna Expression ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Close Association ◽  
Interleukin 1 ◽  
Cell Types ◽  
Tgf Beta ◽  
Specific Stage ◽  
Growth Factor Beta

Using in situ hybridization, we investigated the expression of mRNA for interleukin-1 beta (IL1 beta), interleukin-6 (IL6), and transforming growth factor-beta-1 (TGF beta 1) in sections of developing bone in human osteophytes. The expression was related to the cellular activity of alkaline phosphatase to aid in the identification of pre-osteoblast populations. IL1 beta mRNA was localized in active osteoblasts within distinct areas of intramembranous ossification. However, the expression was sporadic and appeared to occur at a specific stage of the osteoblast life cycle. There was no IL1 beta mRNA expression in any cell types during endochondral ossification. IL6 mRNA expression was located within pre-osteoblasts and in newly differentiated and matrix-secreting osteoblasts; expression was absent or reduced in flattened, inactive osteoblasts. Weak or no IL6 expression was observed in chondroblasts and chondrocytes, respectively. However, there was a close association between IL6 mRNA expression and the differentiation of mesenchymal cells into osteoblasts. TGF beta 1 expression was localized to osteoblasts apposed to bone or cartilage matrix; the intensity of expression correlated with matrix secretion. Chondroblasts and chondrocytes expressed lower but significant levels of TGF beta 1 mRNA; the expression was lost with the progression to calcifying cartilage. The three cytokines studied were differentially expressed both temporally and spatially, suggesting different roles for each in osteoblast and chondrocyte function.

scholarly journals Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth.

1986 ◽  
Vol 163 (5) ◽  
pp. 1037-1050 ◽  
Author(s):  
J H Kehrl ◽  
L M Wakefield ◽  
A B Roberts ◽  
S Jakowlew ◽  
M Alvarez-Mon ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Transforming Growth Factor Beta ◽  
Potential Role ◽  
Transforming Growth Factor ◽  
Cell Types ◽  
Tgf Beta ◽  
Activated T Cells ◽  
Growth Factor Beta

This study examines the potential role of transforming growth factor beta (TGF-beta) in the regulation of human T lymphocyte proliferation, and proposes that TGF-beta is an important autoregulatory lymphokine that limits T lymphocyte clonal expansion, and that TGF-beta production by T lymphocytes is important in T cell interactions with other cell types. TGF-beta was shown to inhibit IL-2-dependent T cell proliferation. The addition of picograms amounts of TGF-beta to cultures of IL-2-stimulated human T lymphocytes suppressed DNA synthesis by 60-80%. A potential mechanism of this inhibition was found. TGF-beta inhibited IL-2-induced upregulation of the IL-2 and transferrin receptors. Specific high-affinity receptors for TGF-beta were found both on resting and activated T cells. Cellular activation was shown to result in a five- to sixfold increase in the number of TGF-beta receptors on a per cell basis, without a change in the affinity of the receptor. Finally, the observations that activated T cells produce TGF-beta mRNA and that TGF-beta biologic activity is present in supernatants conditioned by activated T cells is strong evidence that T cells themselves are a source of TGF-beta. Resting T cells were found to have low to undetectable levels of TGF-beta mRNA, while PHA activation resulted in a rapid increase in TGF-beta mRNA levels (within 2 h). Both T4 and T8 lymphocytes were found to make mRNA for TGF-beta upon activation. Using both a soft agar assay and a competitive binding assay, TGF-beta biologic activity was found in supernatants conditioned by T cells; T cell activation resulted in a 10-50-fold increase in TGF-beta production. Thus, TGF-beta may be an important antigen-nonspecific regulator of human T cell proliferation, and important in T cell interaction with other cell types whose cellular functions are modulated by TGF-beta.

scholarly journals Synthesis of transforming growth factor-beta 1 by megakaryocytes and its localization to megakaryocyte and platelet alpha-granules

Blood ◽  
1990 ◽  
Vol 76 (10) ◽  
pp. 1946-1955 ◽  
Author(s):  
RA Fava ◽  
TT Casey ◽  
J Wilcox ◽  
RW Pelton ◽  
HL Moses ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Messenger Rna ◽  
Transforming Growth Factor ◽  
Immunoperoxidase Technique ◽  
Storage Site ◽  
Tgf Beta ◽  
Growth Factor Beta

We have directly demonstrated that megakaryocytes are a major site of synthesis and storage of transforming growth factor-beta 1 (TGF/beta 1) by combined immunohistochemical, immunocytochemical, and in situ hybridization methods. The presence of TGF/beta 1 messenger RNA (mRNA) in mature megakaryocytes in adult rat spleen and bone marrow (BM) was established by in situ hybridization. Localization of TGF/beta 1 protein to intact alpha-granules of megakaryocytes, its putative storage site, was accomplished in glycol-methacrylate embedded porcine BM with an immunoperoxidase technique and light microscopy. The TGF/beta 1 was sequestered in intracytoplasmic granules in a pattern virtually identical to that of another alpha-granule marker protein, fibrinogen. This observation strongly suggests packaging of TGF/beta 1 into this organelle within megakaryocytes. That TGF/beta 1 mRNA was localized to megakaryocytes suggests that the TGF/beta 1 found in the alpha-granules in platelets originates with megakaryocyte synthesis. The alpha-granule localization of TGF/beta 1, as well as fibrinogen, was also demonstrated in isolated platelets at the ultrastructural level by electronmicroscopy (EM) and postembedding colloidal-gold immunocytochemistry, thus directly demonstrating that alpha-granules are the final storage site for TGF/beta 1 in mature platelets.

Regulated expression and growth inhibitory effects of transforming growth factor-beta isoforms in mouse mammary gland development

Development ◽  
1991 ◽  
Vol 113 (3) ◽  
pp. 867-878 ◽  
Author(s):  
S.D. Robinson ◽  
G.B. Silberstein ◽  
A.B. Roberts ◽  
K.C. Flanders ◽  
C.W. Daniel
Keyword(s):  
Gene Expression ◽  
Mammary Gland ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Slow Release ◽  
Mouse Mammary Gland ◽  
Tgf Beta ◽  
Growth Factor Beta ◽  
Beta 2

Transforming Growth Factor-beta 1 (TGF-beta 1) was previously shown to inhibit reversibly the growth of mouse mammary ducts when administered in vivo by miniature slow-release plastic implants. We now report a comparative analysis of three TGF-beta isoforms with respect to gene expression and localization of protein products within the mouse mammary gland. Our studies revealed overlapping expression patterns of TGF-beta 1, TGF-beta 2 and TGF-beta 3 within the epithelium of the actively-growing mammary end buds during branching morphogenesis, as well as within the epithelium of growth-quiescent ducts. However, TGF-beta 3 was the only isoform detected in myoepithelial progenitor cells (cap cells) of the growing end buds and myoepithelial cells of the mature ducts. During pregnancy, TGF-beta 2 and TGF-beta 3 transcripts increased to high levels, in contrast to TGF-beta 1 transcripts which were moderately abundant; TGF-beta 2 was significantly transcribed only during pregnancy. Molecular hybridization in situ revealed overlapping patterns of expression for the three TGF-beta isoforms during alveolar morphogenesis, but showed that, in contrast to the patterns of TGF-beta 1 and TGF-beta 2 expression, TGF-beta 3 is expressed more heavily in ducts than in alveoli during pregnancy. Developing alveolar tissue and its associated ducts displayed striking TGF-beta 3 immunoreactivity which was greatly reduced during lactation. All three isoforms showed dramatically reduced expression in lactating tissue. The biological effects of active, exogenous TGF-beta 2 and TGF-beta 3 were tested with slow-release plastic implants. These isoforms, like TGF-beta 1, inhibited mammary ductal elongation in situ by causing the disappearance of the proliferating stem cell layer (cap cells) and rapid involution of ductal end buds. None of the isoforms were active in inhibiting alveolar morphogenesis. We conclude that under the limited conditions of these tests, the three mammalian isoforms are functionally equivalent. However, striking differences in patterns of gene expression and in the distribution of immunoreactive peptides suggest that TGF-beta isoforms may have distinct roles in mammary growth regulation, morphogenesis and functional differentiation.

scholarly journals Distribution and modulation of the cellular receptor for transforming growth factor-beta.

1987 ◽  
Vol 105 (2) ◽  
pp. 965-975 ◽  
Author(s):  
L M Wakefield ◽  
D M Smith ◽  
T Masui ◽  
C C Harris ◽  
M B Sporn
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Cell Types ◽  
Tgf Beta ◽  
Cell Type ◽  
Down Regulation ◽  
Growth Factor Beta ◽  
Different Cell Types

Scatchard analyses of the binding of transforming growth factor-beta (TGF-beta) to a wide variety of different cell types in culture revealed the universal presence of high affinity (Kd = 1-60 pM) receptors for TGF-beta on every cell type assayed, indicating a wide potential target range for TGF-beta action. There was a strong (r = +0.85) inverse relationship between the receptor affinity and the number of receptors expressed per cell, such that at low TGF-beta concentrations, essentially all cells bound a similar number of TGF-beta molecules per cell. The binding of TGF-beta to various cell types was not altered by many agents that affect the cellular response to TGF-beta, suggesting that modulation of TGF-beta binding to its receptor may not be a primary control mechanism in TGF-beta action. Similarly, in vitro transformation resulted in only relatively small changes in the cellular binding of TGF-beta, and for those cell types that exhibited ligand-induced down-regulation of the receptor, down-regulation was not extensive. Thus the strong conservation of binding observed between cell types is also seen within a given cell type under a variety of conditions, and receptor expression appears to be essentially constitutive. Finally, the biologically inactive form of TGF-beta, which constitutes greater than 98% of autocrine TGF-beta secreted by all of the twelve different cell types assayed, was shown to be unable to bind to the receptor without prior activation in vitro. It is proposed that this may prevent premature interaction of autocrine ligand and receptor in the Golgi apparatus.

Expression of transforming growth factor beta 2 RNA during murine embryogenesis

Development ◽  
1989 ◽  
Vol 106 (4) ◽  
pp. 759-767 ◽  
Author(s):  
R.W. Pelton ◽  
S. Nomura ◽  
H.L. Moses ◽  
B.L. Hogan
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Post Partum ◽  
Mouse Embryos ◽  
Tgf Beta ◽  
Growth Factor Beta ◽  
Beta 2 ◽  
Temporal And Spatial

We have studied the temporal and spatial expression of transforming growth factor beta 2 (TGF beta 2) RNA in mouse embryos from 10.5 days post coitum (p.c.) to 3 days post partum (p.p.) by in situ hybridization analysis. TGF beta 2 RNA is expressed in a variety of tissues including bone, cartilage, tendon, gut, blood vessels, skin and fetal placenta, and is in general found in the mesenchymal component of these tissues. The expression of TGF beta 2 RNA changes during development in a manner consistent with a role for the gene product in mediating mesenchymal-epithelial interactions.

scholarly journals Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts

1993 ◽  
Vol 122 (1) ◽  
pp. 103-111 ◽  
Author(s):  
A Desmoulière ◽  
A Geinoz ◽  
F Gabbiani ◽  
G Gabbiani
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Mrna Expression ◽  
Granulation Tissue ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Tgf Beta ◽  
Cultured Fibroblasts ◽  
Growth Factor Beta ◽  
Actin Expression

Granulation tissue fibroblasts (myofibroblasts) develop several ultrastructural and biochemical features of smooth muscle (SM) cells, including the presence of microfilament bundles and the expression of alpha-SM actin, the actin isoform typical of vascular SM cells. Myofibroblasts have been proposed to play a role in wound contraction and in retractile phenomena observed during fibrotic diseases. We show here that the subcutaneous administration of transforming growth factor-beta 1 (TGF beta 1) to rats results in the formation of a granulation tissue in which alpha-SM actin expressing myofibroblasts are particularly abundant. Other cytokines and growth factors, such as platelet-derived growth factor and tumor necrosis factor-alpha, despite their profibrotic activity, do not induce alpha-SM actin in myofibroblasts. In situ hybridization with an alpha-SM actin probe shows a high level of alpha-SM actin mRNA expression in myofibroblasts of TGF beta 1-induced granulation tissue. Moreover, TGF beta 1 induces alpha-SM actin protein and mRNA expression in growing and quiescent cultured fibroblasts and preincubation of culture medium containing whole blood serum with neutralizing antibodies to TGF beta 1 results in a decrease of alpha-SM actin expression by fibroblasts in replicative and non-replicative conditions. These results suggest that TGF beta 1 plays an important role in myofibroblast differentiation during wound healing and fibrocontractive diseases by regulating the expression of alpha-SM actin in these cells.

Expression of transforming growth factor-beta receptors during hyperoxia-induced lung injury and repair

1997 ◽  
Vol 273 (2) ◽  
pp. L355-L362 ◽  
Author(s):  
Y. Zhao ◽  
B. J. Gilmore ◽  
S. L. Young
Keyword(s):  
Growth Factor ◽  
Lung Injury ◽  
Mrna Expression ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Rat Lung ◽  
Tgf Beta ◽  
Hyperoxic Exposure ◽  
Growth Factor Beta ◽  
Injury And Repair

Lung injury and repair processes involve many cellular activities, including cell growth, differentiation, and remodeling of extracellular matrix components. Transforming growth factor-beta (TGF-beta) is a major class of signaling peptide growth factors regulating these cellular activities. Type I (T beta RI) and type II (T beta RII) receptors for TGF-beta are transmembrane serine/threonine kinases that are essential for TGF-beta signaling. To gain insight into the possible molecular mechanisms of lung injury and repair, we investigated the expression of T beta RI and T beta RII in an acute hyperoxia-induced model of lung injury and repair. Localization of message expression of T beta RI and T beta RII in oxygen-exposed rat lung tissue was analyzed by using in situ hybridization. T beta RI mRNA expression was found in the interstitium, capillaries, and the alveolar septa of rat lungs exposed for 60 h to 100% oxygen. The distribution of T beta RII mRNA in oxygen-exposed rat lung tissue overlapped the localization of T beta RI mRNA. Temporal changes of T beta RI and T beta RII mRNA expressions in rat lung during hyperoxic exposure and repair were examined by Northern analysis. We found that expression of T beta RI was upregulated in adult rats undergoing prolonged exposure to 100% oxygen, and the increase of T beta RI expression persisted during 2 wk of repair of lung injury. The pattern of T beta RII expression during hyperoxic exposure and repair was distinct from that of T beta RI. The expression of T beta RII increased with a peak at 3 days postexposure and then declined after 7 days of repair. Changes of T beta RI and T beta RII protein expressions in rat lung during hyperoxic exposure and repair were examined further by Western blot analysis, which correlated with the mRNA expression. The results suggest that T beta RI and T beta RII may play important roles during the lung injury and repair by mediating signaling activity of TGF-beta and may regulate interactions between the mesenchyme and the epithelium.

scholarly journals Transforming growth factor beta downregulates interleukin-1 (IL-1)- induced IL-6 production by human monocytes

Blood ◽  
1990 ◽  
Vol 76 (12) ◽  
pp. 2466-2469
Author(s):  
T Musso ◽  
I Espinoza-Delgado ◽  
K Pulkki ◽  
GL Gusella ◽  
DL Longo ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Messenger Rna ◽  
Transforming Growth Factor ◽  
Interleukin 1 ◽  
Dependent Manner ◽  
Human Monocytes ◽  
Tgf Beta ◽  
Growth Factor Beta ◽  
Dose Dependent

We investigated the effects of transforming growth factor beta (TGF beta) on the induction by interleukin-1 beta (IL-1 beta) of IL-6 in human monocytes. We found that IL-1 beta induced IL-6 messenger RNA expression in elutriated monocytes and IL-6 secretion in the supernatant. TGF beta did not induce IL-6. In contrast, TGF beta added to the culture inhibited, in a dose-dependent manner, the induction of IL-6 by IL-1 at the level of messenger RNA and bioactivity. These results show that IL-1 beta is able to stimulate IL-6 production by monocytes, TGF beta, by inhibiting this effect, may play an important role in regulating the IL-1-mediated components of the inflammatory response.

scholarly journals Effect of transforming growth factor-beta 1 on proliferation and induction of hemoglobin accumulation in K-562 cells

Blood ◽  
1989 ◽  
Vol 74 (7) ◽  
pp. 2368-2375 ◽  
Author(s):  
LL Chen ◽  
A Dean ◽  
T Jenkinson ◽  
J Mendelsohn
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Interleukin 1 ◽  
Tgf Beta ◽  
Globin Mrna ◽  
Parent Line ◽  
Concomitant Reduction ◽  
Growth Factor Beta ◽  
K 562 Cells

The effects of transforming growth factor-beta 1 (TGF-beta 1) on proliferation and hemoglobinization in K-562 cells, a human multipotential hematopoietic cell line, were studied. We found that TGF- beta 1 could induce hemoglobin accumulation in K-562 cells. Various clones were selected on the basis of the inducibility of hemoglobinization by TGF-beta 1. One high response clone (no. 1) and one low response clone (no. 8) were studied in detail. Hemoglobin accumulation peaked on day 5 of culture in the presence of TGF-beta 1 (0.5 ng/mL, 20 pmol/L), when 90% of clone 1 cells, 55% of parent line cells, and less than 10% of clone 8 cells contained hemoglobin. There was a concomitant reduction in proliferation of 60% for clone 1, 40% for the parent line, and 30% for the clone 8 on day 5 of culture. Quantitative analysis showed that the hemoglobin contents in clone 1 after 5-day induction by TGF-beta 1 and hemin were 1.0 pg/cell and 2.9 pg/cell, respectively. The hemoglobin induced by TGF-beta 1 showed the same electrophoretic characteristics as the hemoglobin induced by hemin. The expression of epsilon-globin mRNA was minimally detectable in control cells and was induced in both TGF-beta 1 and hemin treated cells. Other cytokines with potential effects on K-562 cell proliferation and differentiation were also studied. Interleukin-1, interleukin-3, interferon alpha, interferon gamma, and inhibin, tested as single agents, showed minimal effects on proliferation. None of these agents could induce hemoglobinization or inhibit the hemoglobinization induced by TGF-beta 1.

Regulation of fibroblast-mediated collagen gel contraction by platelet-derived growth factor, interleukin-1 alpha and transforming growth factor-beta 1

1992 ◽  
Vol 102 (2) ◽  
pp. 315-322 ◽  
Author(s):  
A. Tingstrom ◽  
C.H. Heldin ◽  
K. Rubin
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Interleukin 1 ◽  
Collagen Gel ◽  
Platelet Derived Growth Factor ◽  
Tgf Beta ◽  
Collagen Gels ◽  
Collagen Gel Contraction ◽  
Growth Factor Beta

We have examined the effects of three macrophage-derived cytokines, platelet-derived growth factor (PDGF), transforming growth factor-beta 1 (TGF-beta 1) and interleukin-1 alpha (IL-1 alpha) on the contraction of collagen type I gels populated by human foreskin fibroblasts. Contraction was quantified as loss in gel weight. Both PDGF-AA and PDGF-BB were found to induce a rapid collagen-gel contraction. TGF-beta 1 also stimulated gel contraction but with a delayed onset and at a slower rate than the PDGF-stimulated contraction. Rabbit polyclonal IgGs recognizing PDGF-AA and PDGF-BB, respectively, specifically inhibited the effects of the corresponding PDGF isoforms. However, the stimulatory effect of TGF-beta 1 was not affected by any of the anti-PDGF antibodies. The ability of PDGF to stimulate contraction became less pronounced in collagen gel cultures grown in the absence of growth factors over periods of several days. Under the same conditions, the stimulatory effect of TGF-beta 1 was not reduced. The reduced response to PDGF may be due to reduced tension on fibroblasts growing in collagen gels, since fibroblasts on free-floating gels showed a marked reduction in PDGF-BB-induced PDGF beta-receptor aggregates when compared to fibroblasts on attached collagen gels. IL-1 alpha inhibited initial collagen gel contraction, and at later stages induced a visible degradation of the collagen gels, presumably due to the generation of collagenase activity. The combination of IL-1 alpha and PDGF-BB stimulated initial collagen gel contraction, although less effectively than PDGF-BB alone.(ABSTRACT TRUNCATED AT 250 WORDS)

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