Thrombospondin-1 is not the major activator of TGF-β1 in thrombopoietin-induced myelofibrosis

Blood ◽  
2011 ◽  
Vol 117 (1) ◽  
pp. 246-249 ◽  
Author(s):  
Solène Evrard ◽  
Olivier Bluteau ◽  
Micheline Tulliez ◽  
Philippe Rameau ◽  
Patrick Gonin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Active Form ◽  
Transforming Growth Factor Β1 ◽  
Myeloproliferative Syndrome ◽  
Thrombospondin 1 ◽  
Tgf Β1 ◽  
Important Cytokine

Abstract Transforming growth factor-β1 (TGF-β1) is the most important cytokine involved in the promotion of myelofibrosis. Mechanisms leading to its local activation in the bone marrow environment remain unclear. As a recent study has highlighted the role of thrombospondin-1 (TSP-1) in platelet-derived TGF-β1 activation, we investigated the role of TSP-1 in the TPOhigh murine model of myelofibrosis. Two groups of engrafted mice, WT TPOhigh and Tsp-1–null TPOhigh, were constituted. All mice developed a similar myeloproliferative syndrome and an increase in total TGF-β1 levels in the plasma and in extracellular fluids of marrow and spleen. Surprisingly, we were able to detect the active form of TGF-β1 in Tsp-1–null TPOhigh mice. Accordingly, these mice developed marrow and spleen fibrosis, with intriguingly a higher grade than in WT TPOhigh mice. Our results show that TSP-1 is not the major activator of TGF-β1 in TPO-induced myelofibrosis, suggesting the contribution of another mechanism in the megakaryocyte/platelet compartment.

Upregulation of Thrombospondin 1 Expression in Synovial Tissues and Plasma of Rheumatoid Arthritis: Role of Transforming Growth Factor-β1 toward Fibroblast-like Synovial Cells

2015 ◽  
Vol 42 (6) ◽  
pp. 943-947 ◽  
Author(s):  
Takahisa Suzuki ◽  
Naoki Iwamoto ◽  
Satoshi Yamasaki ◽  
Ayako Nishino ◽  
Yoshikazu Nakashima ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Disease Process ◽  
Transforming Growth Factor Β1 ◽  
Joint Disease ◽  
Synovial Cells ◽  
Thrombospondin 1 ◽  
Synovial Tissues ◽  
Tgf Β1

Objective.To investigate the role of thrombospondin 1 (TSP-1) in RA.Methods.Expression of TSP-1 in synovial tissues was determined by immunohistochemistry. Expression of TSP-1 in rheumatoid fibroblast-like synovial cells (FLS) was investigated by quantitative real-time PCR and ELISA. Correlations among the plasma TSP-1 and other variables in patients with RA were examined.Results.Expression of TSP-1 was increased in rheumatoid synovial tissues. Transforming growth factor-β1 (TGF-β1) clearly increased TSP-1 expression in FLS on both mRNA and protein levels. Changes in plasma TSP-1 were associated with those in 28-joint Disease Activity Score-erythrocyte sedimentation rate and plasma TGF-β1.Conclusion.TSP-1 might be critically involved in the disease process of RA through the TGF-β1/TSP-1 axis.

scholarly journals Transforming growth factor-β1 modulates responses of CD34+ cord blood cells to stromal cell-derived factor-1/CXCL12

Blood ◽  
2005 ◽  
Vol 106 (2) ◽  
pp. 485-493 ◽  
Author(s):  
Sunanda Basu ◽  
Hal E. Broxmeyer
Keyword(s):  
Bone Marrow ◽  
Growth Factor ◽  
Cord Blood ◽  
Progenitor Cells ◽  
Stromal Cell ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Cd34 Cells ◽  
Stromal Cell Derived Factor ◽  
Tgf Β1

Abstract Disruption of stromal cell-derived factor-1 (SDF-1/CXCL12 [CXC chemokine ligand 12]) interaction leads to mobilization of stem/progenitor cells from bone marrow to circulation. However, prolonged exposure of CD34+ cells to SDF-1 desensitizes them to SDF-1. So how do cells remain responsive to SDF-1 in vivo when they are continuously exposed to SDF-1? We hypothesized that one or more mechanisms mediated by cytokines exist that could modulate SDF-1 responsiveness of CD34+ cells and the desensitization process. We considered transforming growth factor-β1 (TGF-β1) a possible candidate, since TGF-β1 has effects on CD34+ cells and is produced by stromal cells, which provide niches for maintenance and proliferation of stem/progenitor cells. TGF-β1 significantly restored SDF-1–induced chemotaxis and sustained adhesion responses in cord blood CD34+ cells preexposed to SDF-1. Effects of TGF-β1 were dependent on the dose and duration of TGF-β1 pretreatment. Phosphorylation of extracellular signal-regulated kinase 1 (Erk1)/Erk2 was implicated in TGF-β1 modulation of migratory and adhesion responses to SDF-1. Our results indicate that low levels of TGF-β1 can modulate SDF-1 responsiveness of CD34+ cells and thus may facilitate SDF-1–mediated retention and nurturing of stem/progenitor cells in bone marrow.

Down-Regulation of Toll-Like Receptor 4 Expression in Transforming Growth Factor β1 Treated Murine Dendritic Cells: Implications of Maturation Resistant to Lipopolysaccharide.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3803-3803
Author(s):  
Maofang Lin ◽  
Haibo Mou ◽  
Hong Cen
Keyword(s):  
Bone Marrow ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Brdu Incorporation ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Murine Bone Marrow ◽  
Gm Csf ◽  
Tgf Β1

Abstract Evidences accumulated that immature dendritic cell (iDC) could inhibit alloantigen-specific T cell responses and prolong the survival time of allografts. However, the tolerogenic properties of these iDCs were often unstable or inconsistent because of in vivo maturation, such as lipopolysaccharide (LPS) stimulating. Toll-like receptor 4(TLR4) has been reported to act as a receptor for LPS and LPS can stimulate iDC to mature DC (mDC) via TLR4 signal transduction pathway. In this study, we investigated the effects of transforming growth factor β1 on murine bone marrow derived DCs. Murine bone marrow cells were cultured with GM-CSF and TGF-β1 to generate TGF-β1 treated DCs (TGFβ-DCs). Compared to iDCs cultured by GM-CSF alone, the TGFβ-DCs had no significant alterations in ultrastructure after LPS stimulation. Surface expression of CD80, CD86, CD40, MHC-II were inhibited by addition of TGF-β1, especially in CD80, CD86 (p<0.05). Furthermore, the iDCs were sensitive to further maturation in response to LPS by showing increased levels of MHC class II, CD80, CD86 and CD40. In marked contrast, TGF-β1 prevented this LPS-mediated maturation and maintained the cells in the immature state, with low levels of surface costimulatory molecules expression. Using BrdU incorporation method, after 96 h mix lymphocyte reaction, TGFβ-DCs had weaker allogeneic stimulating capacity than iDCs. Importantly, LPS stimulating strongly promoted the allostimulatory capacity of iDCs, whereas only slightly affected TGFβ-DCs. TGFβ-DCs also showed decreased IL-12p70 production and impaired NF-κB activation after LPS stimulation. We also found the expression of TLR4 mRNA on TGFβ-DCs was weaker than that on iDCs by RT-PCR. Moreover, the results of flow cytometry revealed the positive expression percentages of TLR4/MD2 complex on iDCs and TGFβ-DCs were (51.8±3.89% vs. 15.7±4.13%, p<0.01) and the mean fluorescence intensities (MFIs) were (2.37±0.26 vs. 1.36±0.17, p<0.05). These results agreed with previous findings that TGFβ-DCs responded weakly to LPS. In summary, TGFβ-DC is resistant to maturation stimulus (LPS) and might have some correlation with the down-modulation of TLR4 expression.

Role of transforming growth factor-β1 (TGF-β1) in endotoxin-induced hepatic failure after extensive hepatectomy in rats

2005 ◽  
Vol 11 (1) ◽  
pp. 33-39 ◽  
Author(s):  
Noboru Yoshimoto ◽  
Shinji Togo ◽  
Toru Kubota ◽  
Nobuyuki Kamimukai ◽  
Shuji Saito ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatic Failure ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Extensive Hepatectomy ◽  
Tgf Β1

Role of tumor-derived transforming growth factor-β1 (TGF-β1) in site-dependent tumorigenicity of murine ascitic lymphosarcoma

2005 ◽  
Vol 54 (9) ◽  
pp. 837-847 ◽  
Author(s):  
V. S. Thakur ◽  
B. Shankar ◽  
S. Chatterjee ◽  
S. Premachandran ◽  
K. B. Sainis
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Tgf Β1

scholarly journals Role of transforming growth factor-β1 (TGF-β1) in endotoxin-induced hepatic failure after extensive hepatectomy in rats

2005 ◽  
Vol 11 (1) ◽  
pp. 33-39 ◽  
Author(s):  
Noboru Yoshimoto ◽  
Shinji Togo ◽  
Toru Kubota ◽  
Nobuyuki Kamimukai ◽  
Shuji Saito ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatic Failure ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Extensive Hepatectomy ◽  
Tgf Β1

Porcine thyroid follicular cells in monolayer culture activate the iodide-responsive precursor form of transforming growth factor-β1

1995 ◽  
Vol 144 (1) ◽  
pp. 67-73 ◽  
Author(s):  
A J Cowin ◽  
S P Bidey
Keyword(s):  
Growth Factor ◽  
Monolayer Culture ◽  
Transforming Growth Factor ◽  
Thymidine Incorporation ◽  
Active Form ◽  
Transforming Growth Factor Β1 ◽  
Biologically Active ◽  
Follicular Cells ◽  
Thyroid Follicular Cells ◽  
Tgf Β1

Abstract The release of latent transforming growth factor-β1 (TGFβ1), and conversion to the biologically active peptide, has been investigated in porcine thyroid follicular cells maintained in primary monolayer culture. Analysis by radioreceptor assay of medium conditioned for 72 h by subconfluent thyroid monolayers showed that a high proportion of the expressed TGF-β1 peptide was in the active form. Medium conditioned by iodide (10 aμmol/l)treated follicular cells contained higher levels of both active and total TGF-β1 than were present in medium conditioned by untreated cells. Exposure of cells to iodide also led to a marked decrease in [methyl-3H]thymidine incorporation that was relieved by immunoadsorption with a neutralizing antiserum against the active form of TGFβ1. Inclusion of a low dose (80 units/l) of porcine plasmin led to a small increase in incorporation of [methyl3H]thymidine, while higher doses of plasmin (1250–5000 units/l) or plasminogen (100 mg/l) significantly reduced [methyl-3H]thymidine incorporation. This inhibition was effectively reversed by immunoadsorption of TGF-β1 from the medium during the test incubations. The study therefore provides direct evidence for a stimulatory role of thyroidal iodide in enhancing the release of latent TGF-β1 peptide, and suggests that in normal thyroid follicular cells, as in other TGF-β1 producing epithelia, post-secretory processing to the biologically active molecule occurs through an endogenous cellular mechanism. It appears likely that plasmin, generated locally within the thyroid follicular microenvironment, may play a fundamental role in effecting this conversion. Journal of Endocrinology (1995) 144, 67–73

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