scholarly journals Transforming growth factor-beta1 is a potent inhibitor of interleukin-1beta action in whole ovarian dispersates

1999 ◽  
Vol 160 (3) ◽  
pp. 415-423 ◽  
Author(s):  
SG Derman ◽  
S Kol ◽  
I Ben-Shlomo ◽  
CE Resnick ◽  
RM Rohan ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Glucose Consumption ◽  
Type I ◽  
Dependent Manner ◽  
Transforming Growth Factor Beta1 ◽  
Organ Systems ◽  
Steady State Levels ◽  
Interleukin 1Beta ◽  
Dose Dependent

Transforming growth factor beta1 (TGFbeta1) acts as an inhibitor of the actions of interleukin-1beta (IL-1beta) in various organ systems. In order better to understand the inter|P-actions between these polypeptides in the ovary, we evaluated the effect of TGFbeta1 co-treatment on various IL-1beta-mediated actions in cultures of whole ovarian dispersates. Treatment with IL-1beta enhanced media accumulation of nitrites (4.8-fold), prostaglandin E2 (PGE2, 3. 9-fold) and lactate (2.0-fold), and enhanced glucose consumption (2. 1-fold). Treatment with TGFbeta1 alone did not significantly affect any of these parameters. However, the addition of TGFbeta1 inhibited IL-1beta-stimulated nitrite (100%), PGE2 (44%) and lactate (78%) accumulation and inhibited IL-1beta-stimulated glucose consumption (74%) in a dose-dependent manner. The addition of TGFbeta1 also suppressed the steady-state levels of IL-1beta-stimulated IL-1beta, type I IL-1 receptor and IL-1 receptor antagonist transcripts (98, 67 and 83% inhibition respectively). These data suggest that TGFbeta1 is capable of inhibiting several IL-1beta-stimulated endpoints. Since IL-1 has been identified as a possible proinflammatory mediator of ovulation and TGFbeta has been implicated as a promotor of fibrosis and healing, we speculate that IL-1 and TGFbeta might play antagonistic roles in the normal ovulatory sequence.

Influence of transforming growth factor beta1 (TGF-beta1) on the behaviour of porcine thyroid epithelial cells in primary culture through thrombospondin-1 synthesis

1999 ◽  
Vol 112 (9) ◽  
pp. 1405-1416
Author(s):  
D. Claisse ◽  
I. Martiny ◽  
B. Chaqour ◽  
Y. Wegrowski ◽  
E. Petitfrere ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Follicle Cells ◽  
Dependent Manner ◽  
Transforming Growth Factor Beta1 ◽  
Thyroid Cells ◽  
Amino Terminal ◽  
Thrombospondin 1 ◽  
Inhibitor Of Protein Synthesis

Transforming growth factor beta1 (TGF-beta1) is a secreted polypeptide that is thought to play a major role in the regulation of folliculogenesis and differentiation of thyroid cells. On porcine thyroid follicular cells cultured on plastic substratum, TGF-beta1, in a concentration-dependent way, promoted the disruption of follicles, cell spreading, migration and confluency by a mechanism that did not involve cell proliferation. TGF-beta1 strongly activated the production of thrombospondin-1 and (alpha)vbeta3 integrin in a concentration-dependent manner whereas the expression of thyroglobulin was unaffected. Anisomycin, an inhibitor of protein synthesis, inhibited the effect of TGF-beta1 on cell organization. Thrombospondin-1 reproduced the effect of TGF-beta1. In the presence of thrombospondin-1 cells did not organize in follicle-like structures but, in contrast, spreaded and reached confluency independently of cell proliferation. This effect is suppressed by an RGD-containing peptide. The adhesive properties of thrombospondin-1 for thyroid cells were shown to be mediated by both the amino-terminal heparin-binding domain and the RGD domain of thrombospondin-1. Adhesion was shown to involve (alpha)vbeta3 integrin. The results show that TGF-beta1 exerted an influence upon function and behaviour of follicle cells partly mediated by the synthesis of thrombospondin-1 and of its receptor (alpha)vbeta3 integrin.

scholarly journals NEDD4-2 (neural precursor cell expressed, developmentally down-regulated 4-2) negatively regulates TGF-β (transforming growth factor-β) signalling by inducing ubiquitin-mediated degradation of Smad2 and TGF-β type I receptor

2005 ◽  
Vol 386 (3) ◽  
pp. 461-470 ◽  
Author(s):  
Go KURATOMI ◽  
Akiyoshi KOMURO ◽  
Kouichiro GOTO ◽  
Masahiko SHINOZAKI ◽  
Keiji MIYAZAWA ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Ubiquitin Ligases ◽  
Transforming Growth Factor Β ◽  
Precursor Cell ◽  
Neural Precursor ◽  
Type I ◽  
Dependent Manner ◽  
E3 Ubiquitin Ligases ◽  
Neural Precursor Cell

Inhibitory Smad, Smad7, is a potent inhibitor of TGF-β (transforming growth factor-β) superfamily signalling. By binding to activated type I receptors, it prevents the activation of R-Smads (receptor-regulated Smads). To identify new components of the Smad pathway, we performed yeast two-hybrid screening using Smad7 as bait, and identified NEDD4-2 (neural precursor cell expressed, developmentally down-regulated 4-2) as a direct binding partner of Smad7. NEDD4-2 is structurally similar to Smurfs (Smad ubiquitin regulatory factors) 1 and 2, which were identified previously as E3 ubiquitin ligases for R-Smads and TGF-β superfamily receptors. NEDD4-2 functions like Smurfs 1 and 2 in that it associates with TGF-β type I receptor via Smad7, and induces its ubiquitin-dependent degradation. Moreover, NEDD4-2 bound to TGF-β-specific R-Smads, Smads 2 and 3, in a ligand-dependent manner, and induced degradation of Smad2, but not Smad3. However, in contrast with Smurf2, NEDD4-2 failed to induce ubiquitination of SnoN (Ski-related novel protein N), although NEDD4-2 bound to SnoN via Smad2 more strongly than Smurf2. We showed further that overexpressed NEDD4-2 prevents transcriptional activity induced by TGF-β and BMP, whereas silencing of the NEDD4-2 gene by siRNA (small interfering RNA) resulted in enhancement of the responsiveness to TGF-β superfamily cytokines. These data suggest that NEDD4-2 is a member of the Smurf-like C2-WW-HECT (WW is Trp-Trp and HECT is homologous to the E6-accessory protein) type E3 ubiquitin ligases, which negatively regulate TGF-β superfamily signalling through similar, but not identical, mechanisms to those used by Smurfs.

scholarly journals Studies on the Biological Effects of Ozone: 10. Release of Factors from Ozonated Human Platelets

1999 ◽  
Vol 8 (4-5) ◽  
pp. 205-209 ◽  
Author(s):  
G. Valacchi ◽  
Velio Bocci
Keyword(s):  
Platelet Aggregation ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Platelet Rich Plasma ◽  
Biological Effects ◽  
Transforming Growth Factor Β1 ◽  
Human Platelets ◽  
Dependent Manner ◽  
Dose Dependent ◽  
Tgf Β1

In a previous work we have shown that heparin, in the presence of ozone (O3), promotes a dose-dependent platelet aggregation, while after Ca2+chelation with citrate, platelet aggregation is almost negligible. These results led us to think that aggregation may enhance the release of platelet components. We have here shown that indeed significantly higher amount of platelet-derived growth factor (PDGF), transforming growth factor β1 (TGF-β1) and interleukin-8(IL-8) are released in a dose-dependent manner after ozonation of heparinised platelet-rich plasma samples. These findings may explain the enhanced healing of torpid ulcers in patients with chronic limbischemia treated with O3autohaemoteraphy (O3-AHT).

scholarly journals BMP-4 inhibits follicle-stimulating hormone secretion in ewe pituitary

2005 ◽  
Vol 186 (1) ◽  
pp. 109-121 ◽  
Author(s):  
M-O Faure ◽  
L Nicol ◽  
S Fabre ◽  
J Fontaine ◽  
N Mohoric ◽  
...  
Keyword(s):  
Growth Factor ◽  
Mrna Expression ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Hormone Secretion ◽  
Inhibitory Effect ◽  
Type I ◽  
Mrna Levels ◽  
Dependent Manner

Activins and inhibins, members of the transforming growth factor-beta family are able to stimulate and inhibit, respectively, FSH synthesis and release. Other members of this superfamily, the bone morphogenetic proteins (BMPs), may also affect FSH synthesis in the mouse. The aim of this work was to determine whether BMPs are expressed in the ovine pituitary and whether they play a role in the regulation of FSH release. The mRNAs encoding BMP-2, BMP-4, BMP-7 and the oocyte-derived growth factor, growth differentiation factor (GDF)-9 were detected in the pituitaries of cyclic ewes by reverse-transcriptase PCR, as well as the mRNAs encoding the BMP type I receptors, BMPR-IA (activin-receptor-like kinase (ALK)-3) and BMPR-IB (ALK-6), and type II receptors (BMPR-II). Immunolabeling of pituitary sections revealed the presence of BMPR-IA (ALK-3) and BMPR-II in gonadotrope cells. To investigate the potential effects of BMPs on FSH secretion, ewe pituitary cell cultures were treated with BMP-4 (10−11 M to 10−9 M) for 48 h. Interestingly, FSH release was decreased in a dose-dependent manner. At 10−9 M BMP-4 both FSH concentration and FSHβ mRNA expression were reduced by 40% of control values. In contrast, there was no inhibitory effect on either LH or LHβ mRNA expression. A similar result was found with BMP-6. BMP-4 triggered the phosphorylation of Smad1, suggesting that the effect of BMP-4 on FSH secretion is due to the activation of the BMPs signaling pathway. Furthermore, BMP-4 blocked the stimulatory effect of activin on both FSH release and FSHβ mRNA and amplified the suppression of FSH release and FSHβ mRNA levels induced by 17β-estradiol. These results indicate that a functional BMP system operates within the sheep pituitary, at least in vitro, to decrease FSH release and to modulate the effect of activin.

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 Medroxyprogesterone reverses tolerable dose metformin-induced inhibition of invasion via matrix metallopeptidase-9 and transforming growth factor-β1 in KLE endometrial cancer cells

2019 ◽  
Author(s):  
Dong Hoon Suh ◽  
Sunray Lee ◽  
Hyun-Sook Park ◽  
Noh Hyun Park
Keyword(s):  
Endometrial Cancer ◽  
Growth Factor ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cell Invasion ◽  
Transforming Growth Factor ◽  
Dependent Manner ◽  
Matrix Metallopeptidase ◽  
Dose Dependent ◽  
Tgf Β1

AbstractThis study was performed to evaluate the anticancer effects of tolerable doses of metformin with or without medroxyprogesterone (MPA) in endometrial cancer cells. Cell viability, cell invasion, and levels of matrix metallopeptidase (MMP) and transforming growth factor (TGF)-β1 were analyzed using three human endometrial adenocarcinoma cell lines (Ishikawa, KLE, and USPC) after treatment with different dose combinations of MPA (0, 10 μM) and metformin (0, 100, 1000 μM). Combining metformin (0, 100, 1000 μM) and 10 μM MPA induced significantly decreased cell viability in a time- and dose-dependent manner in Ishikawa cells, but not in KLE and USPC cells. There was no dose- or time-dependent cell growth inhibition, or positive western blot results for the expression of progesterone receptors and phospho-AMPKa, following treatment with any combination of metformin (0, 100, 1000 μM) and 10 μM MPA in KLE and USPC cells. In KLE cells, metformin treatment alone significantly inhibited cell invasion in a dose-dependent manner (1.31±0.05, 0.94±0.04, 0.83±0.05 at 0, 100 μM, 1000 μM, respectively; p<0.0005). The inhibitory effect of metformin was reversed to create a stimulating effect when metformin was combined with 10 μM MPA (1.10±0.05, 1.42±0.18, 1.41±0.26 at 0, 100, 1000 μM, respectively; p<0.005). MMP-9 and TGF-β1 showed similar trends in terms of cell invasion in KLE cells. In conclusion, the anti-invasive effect of metformin in KLE cells was completely reversed to the state of no treatment by the addition of MPA; this might be mediated through MMP-9 and TGF-β1. Our study suggests the possibility of these combinations doing harm, rather than good, under some conditions.

scholarly journals Effect of cytokines and growth factors on the secretion of inhibin A, activin A and follistatin by term placental villous trophoblasts in culture

2001 ◽  
pp. 505-511 ◽  
Author(s):  
A Mohan ◽  
J Asselin ◽  
IL Sargent ◽  
NP Groome ◽  
S Muttukrishna
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Culture Media ◽  
Activin A ◽  
Maternal Serum ◽  
Tnf Alpha ◽  
Dependent Manner ◽  
Inhibin A ◽  
Dose Dependent

OBJECTIVE: Maternal serum inhibin A and activin A are higher in pre-eclampsia than in normal pregnancy. The placenta is a source of these proteins in pregnancy. The aim of this study was to investigate the effect of growth factors and proinflammatory cytokines that are raised in pre-eclampsia on the secretion of dimeric inhibin A, activin A and follistatin by villous cytotrophoblasts in culture. DESIGN AND METHODS: Villous cytotrophoblasts were prepared from term placentae and cultured in serum-free media. Cells were treated with increasing concentrations of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, transforming growth factor (TGF)-beta1, granulocyte and monocyte colony-stimulating factor (GMCSF), inhibin A, activin A and follistatin for 2 days. Culture supernatants were assayed for human chorionic gonadotrophin (hCG), inhibin A, activin A and follistatin as appropriate. Experiments were repeated at least three times with each cytokine or growth factor and the data pooled. RESULTS: Cytotrophoblasts syncytialise and spontaneously secrete hCG, inhibin A and activin A in culture. Follistatin levels were <20 pg/ml in most experiments. Activin A secretion was increased in culture in a dose-dependent manner by IL-1beta (approximately 150%, P<0.05), TNF-alpha (approximately 35%, P=0.02) and GMCSF (approximately 100%, P<0.01). hCG secretion was inhibited in a dose-dependent manner by TNF-alpha (50%, P<0.05). Inhibin A was stimulated by IL-1beta ( approximately 30%, P=0.05). Inhibin A, activin A, follistatin or TGF-beta1 did not have a significant effect on any measured parameters. CONCLUSIONS: These data show that inflammatory cytokines increase the secretion of activin A by trophoblasts in culture. The presence of very low levels, or no follistatin (<20 pg/ml) in the culture media suggests 'free' activin A could have autocrine/paracrine effects on cytotrophoblasts. Inhibin A secretion was stimulated by IL-1beta. However, absence of an effect by the other cytokines investigated on inhibin A in this study suggests that the mechanism(s) involved in increasing maternal circulating levels of inhibin A and activin A in pre-eclampsia are controlled differentially.

scholarly journals Transforming Growth Factor-β Induces Nuclear Import of Smad3 in an Importin-β1 and Ran-dependent Manner

2001 ◽  
Vol 12 (4) ◽  
pp. 1079-1091 ◽  
Author(s):  
Akira Kurisaki ◽  
Shingo Kose ◽  
Yoshihiro Yoneda ◽  
Carl-Henrik Heldin ◽  
Aristidis Moustakas
Keyword(s):  
Growth Factor ◽  
Nuclear Import ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Structural Basis ◽  
Type I ◽  
Dependent Manner ◽  
Permeabilized Cells ◽  
Terminal Domain

Smad proteins are cytoplasmic signaling effectors of transforming growth factor-β (TGF-β) family cytokines and regulate gene transcription in the nucleus. Receptor-activated Smads (R-Smads) become phosphorylated by the TGF-β type I receptor. Rapid and precise transport of R-Smads to the nucleus is of crucial importance for signal transduction. By focusing on the R-Smad Smad3 we demonstrate that 1) only activated Smad3 efficiently enters the nucleus of permeabilized cells in an energy- and cytosol-dependent manner. 2) Smad3, via its N-terminal domain, interacts specifically with importin-β1 and only after activation by receptor. In contrast, the unique insert of exon3 in the N-terminal domain of Smad2 prevents its association with importin-β1. 3) Nuclear import of Smad3 in vivo requires the action of the Ran GTPase, which mediates release of Smad3 from the complex with importin-β1. 4) Importin-β1, Ran, and p10/NTF2 are sufficient to mediate import of activated Smad3. The data describe a pathway whereby Smad3 phosphorylation by the TGF-β receptor leads to enhanced interaction with importin-β1 and Ran-dependent import and release into the nucleus. The import mechanism of Smad3 shows distinct features from that of the related Smad2 and the structural basis for this difference maps to the divergent sequences of their N-terminal domains.

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