Transforming growth factor–β1 in supernatants from stored red blood cells inhibits neutrophil locomotion

Blood ◽  
2003 ◽  
Vol 102 (3) ◽  
pp. 1100-1107 ◽  
Author(s):  
Massimo Ghio ◽  
Luciano Ottonello ◽  
Paola Contini ◽  
Massimo Amelotti ◽  
Clemente Mazzei ◽  
...  
Keyword(s):  
Growth Factor ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Fas Ligand ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Increased Risk ◽  
High Dilutions ◽  
Formyl Peptides ◽  
Tgf Β1

Abstract Studies comparing transfusion and nontransfusion patients suggest an increased risk of postoperative infections in transfusion groups. Supernatants of blood components have been shown to affect the function of T lymphocytes and natural killer cells. Here, we found that supernatants from stored red blood cells (RBCs) inhibit human neutrophil migration in response to formyl peptides and stimulate neutrophil locomotion. These effects can be observed with high dilutions of RBC supernatants, such as 1:5 × 106 (vol/vol), able to trigger locomotion as well as desensitization of the cells to alternative chemoattractants. The phenomenon might be mediated by chemoattractants present in the supernatants. As RBC supernatants failed to mobilize intracellular free calcium, the chemoattractants should belong to the group of pure chemoattractants, that is, soluble Fas ligand (sFasL) and transforming growth factor–β1 (TGF-β1), known to act without increasing calcium levels. Recombinant TGF-β1, but not sFasL, was found to reproduce the ability of RBC supernatants to both inhibit neutrophil response to formyl peptides and stimulate neutrophil locomotion. Moreover, TGF-β1–immunodepleted supernatants did not display neutrophil-directed activities. Finally, RBC supernatants from RBCs stored after depletion of leukocytes were incapable of affecting neutrophil function. With neutrophils acting as a first-line antimicrobial defense, the ability, shown here, of high dilutions of RBC supernatants to inhibit neutrophil chemotaxis through TGF-β1 may be a relevant determinant of infections in the postoperative period for transfusion patients. Consistently, the neutrophil chemotactic response to formyl peptide was inhibited by the plasma obtained from 5 transfusion patients.

scholarly journals Transforming Growth Factor β1 Inhibits Fas Ligand Expression and Subsequent Activation-induced Cell Death in T Cells via Downregulation of c-Myc

1999 ◽  
Vol 189 (2) ◽  
pp. 231-239 ◽  
Author(s):  
Laurent Genestier ◽  
Shailaja Kasibhatla ◽  
Thomas Brunner ◽  
Douglas R. Green
Keyword(s):  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Growth Factor ◽  
Fas Ligand ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
T Cell Response ◽  
Activation Induced Cell Death ◽  
Tgf Β1

Activation-induced cell death (AICD) is a process that regulates the size and the duration of the primary immune T cell response. In this report, we investigated the mechanisms involved in the regulation of AICD by transforming growth factor β1 (TGF-β1). We found that TGF-β1 decreased apoptosis of human T cells or T cell hybridomas after activation by anti-CD3. This decrease was associated with inhibition of Fas (Apo-1/CD95) ligand (FasL) expression, whereas Fas signaling was not affected by TGF-β1. In parallel, TGF-β1 inhibited c-Myc expression in T cell hybridomas, and ectopic expression of a chimeric molecule composed of c-Myc and the steroid binding domain of the estrogen receptor (Myc-ER) blocked both the inhibition of FasL and the decrease of AICD induced by TGF-β1, providing that 4-hydroxytamoxifen was present. These results identify one mechanism by which TGF-β1 blocks AICD to allow the clonal expansion of effector T cells and the generation of memory T cells during immune responses.

Concentration of platelets and growth factors in canine autologous conditioned plasma

2011 ◽  
Vol 24 (02) ◽  
pp. 122-125 ◽  
Author(s):  
M. Stief ◽  
J. Gottschalk ◽  
J.-C. Ionita ◽  
A. Einspanier ◽  
G. Oechtering ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Blood Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Platelet Derived Growth Factor ◽  
Significant Difference ◽  
Transforming Growth Factor Β2 ◽  
Endothelial Growth Factor ◽  
Tgf Β1

Summary Objectives: To report the concentration of blood cells and selected growth factors in canine autologous conditioned plasma (ACP). Methods: The density of blood cells in whole blood (WB), ACP and standard plasma preparation (SP) of 10 healthy mature dogs was determined. In both ACP and SP, the concentration of insulin-like growth factor-1 (IGF-1), epidermal growth factor, vascular endothelial growth factor, platelet-derived growth factor-AA, platelet-derived growth factor-AB, platelet-derived growth factor-BB, transforming growth factor-β1 (TGF-β1), and transforming growth factor-β2 was measured using the ELISA technique. In another ten dogs, ACP was prepared using an ultra-soft spinning protocol, and again blood cell density was compared to that obtained in WB. Results: The density of platelets in ACP was significantly higher than that in SP (p = 0.0002), but there was not any significant difference between ACP and WB, nor between WB and ACP prepared using softer centrifugations. Interestingly, only for IGF-1, PDGFBB, and TGF-β1 could reliable measurements be obtained, showing a significant increase in PDGF-BB and TGF-β1 concentrations in ACP compared to SP (p = 0.001, p = 0.0028). Regarding IGF-1 content, there was not any significant difference between ACP and SP. Clinical significance: Canine ACP prepared according to the manufacturer’s recommendations, or by using a softer spin does not show the same specifications as human ACP, which shows a doubling in platelet count compared to WB. Even though canine ACP has a similar number of platelets per injected volume and consequently, probably the same amount of injected growth factors than WB, application of canine ACP would not be associated with the proinflammatory potential reported for WB, as it is almost free of erythrocytes and nucleated cells.

scholarly journals JNK and p38 Inhibitors Prevent Transforming Growth Factor-β1-Induced Myofibroblast Transdifferentiation in Human Graves’ Orbital Fibroblasts

2021 ◽  
Vol 22 (6) ◽  
pp. 2952
Author(s):  
Tzu-Yu Hou ◽  
Shi-Bei Wu ◽  
Hui-Chuan Kau ◽  
Chieh-Chih Tsai
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Mapk Pathway ◽  
Transforming Growth Factor Β1 ◽  
Tissue Growth ◽  
Mitogen Activated Protein Kinase ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Western Blots ◽  
Orbital Fibroblasts ◽  
Tgf Β1

Transforming growth factor-β1 (TGF-β1)-induced myofibroblast transdifferentiation from orbital fibroblasts is known to dominate tissue remodeling and fibrosis in Graves’ ophthalmopathy (GO). However, the signaling pathways through which TGF-β1 activates Graves’ orbital fibroblasts remain unclear. This study investigated the role of the mitogen-activated protein kinase (MAPK) pathway in TGF-β1-induced myofibroblast transdifferentiation in human Graves’ orbital fibroblasts. The MAPK pathway was assessed by measuring the phosphorylation of p38, c-Jun N-terminal kinase (JNK), and extracellular-signal-regulated kinase (ERK) by Western blots. The expression of connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), and fibronectin representing fibrogenesis was estimated. The activities of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) responsible for extracellular matrix (ECM) metabolism were analyzed. Specific pharmacologic kinase inhibitors were used to confirm the involvement of the MAPK pathway. After treatment with TGF-β1, the phosphorylation levels of p38 and JNK, but not ERK, were increased. CTGF, α-SMA, and fibronectin, as well as TIMP-1 and TIMP-3, were upregulated, whereas the activities of MMP-2/-9 were inhibited. The effects of TGF-β1 on the expression of these factors were eliminated by p38 and JNK inhibitors. The results suggested that TGF-β1 could induce myofibroblast transdifferentiation in human Graves’ orbital fibroblasts through the p38 and JNK pathways.

scholarly journals Transforming growth factor-β1-induced N-cadherin drives cell–cell communication through connexin43 in osteoblast lineage

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Yueyi Yang ◽  
Wenjing Liu ◽  
JieYa Wei ◽  
Yujia Cui ◽  
Demao Zhang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Gap Junction ◽  
Cell Line ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Cx43 Expression ◽  
Mc3t3 Cell ◽  
Primary Osteoblasts ◽  
Tgf Β1 ◽  
Cell Cell

AbstractGap junction (GJ) has been indicated to have an intimate correlation with adhesion junction. However, the direct interaction between them partially remains elusive. In the current study, we aimed to elucidate the role of N-cadherin, one of the core components in adhesion junction, in mediating connexin 43, one of the functional constituents in gap junction, via transforming growth factor-β1(TGF-β1) induction in osteoblasts. We first elucidated the expressions of N-cadherin induced by TGF-β1 and also confirmed the upregulation of Cx43, and the enhancement of functional gap junctional intercellular communication (GJIC) triggered by TGF-β1 in both primary osteoblasts and MC3T3 cell line. Colocalization analysis and Co-IP experimentation showed that N-cadherin interacts with Cx43 at the site of cell–cell contact. Knockdown of N-cadherin by siRNA interference decreased the Cx43 expression and abolished the promoting effect of TGF-β1 on Cx43. Functional GJICs in living primary osteoblasts and MC3T3 cell line were also reduced. TGF-β1-induced increase in N-cadherin and Cx43 was via Smad3 activation, whereas knockdown of Smad3 signaling by using siRNA decreased the expressions of both N-cadherin and Cx43. Overall, these data indicate the direct interactions between N-cadherin and Cx43, and reveal the intervention of adhesion junction in functional gap junction in living osteoblasts.

scholarly journals Transforming Growth Factor β1 (TGF-β1) Promotes Endothelial Cell Survival during In Vitro Angiogenesis via an Autocrine Mechanism Implicating TGF-α Signaling

2001 ◽  
Vol 21 (21) ◽  
pp. 7218-7230 ◽  
Author(s):  
Francesc Viñals ◽  
Jacques Pouysségur
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Cell Survival ◽  
Network Formation ◽  
Egf Receptor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
In Vitro Angiogenesis ◽  
Tgf Β1

ABSTRACT Mouse capillary endothelial cells (1G11 cell line) embedded in type I collagen gels undergo in vitro angiogenesis. Cells rapidly reorganize and form capillary-like structures when stimulated with serum. Transforming growth factor β1 (TGF-β1) alone can substitute for serum and induce cell survival and tubular network formation. This TGF-β1-mediated angiogenic activity depends on phosphatidylinositol 3-kinase (PI3K) and p42/p44 mitogen-activated protein kinase (MAPK) signaling. We showed that specific inhibitors of either pathway (wortmannin, LY-294002, and PD-98059) all suppressed TGF-β1-induced angiogenesis mainly by compromising cell survival. We established that TGF-β1 stimulated the expression of TGF-α mRNA and protein, the tyrosine phosphorylation of a 170-kDa membrane protein representing the epidermal growth factor (EGF) receptor, and the delayed activation of PI3K/Akt and p42/p44 MAPK. Moreover, we showed that all these TGF-β1-mediated signaling events, including tubular network formation, were suppressed by incubating TGF-β1-stimulated endothelial cells with a soluble form of an EGF receptor (ErbB-1) or tyrphostin AG1478, a specific blocker of EGF receptor tyrosine kinase. Finally, addition of TGF-α alone poorly stimulated angiogenesis; however, by reducing cell death, it strongly potentiated the action of TGF-β1. We therefore propose that TGF-β1 promotes angiogenesis at least in part via the autocrine secretion of TGF-α, a cell survival growth factor, activating PI3K/Akt and p42/p44 MAPK.

scholarly journals Transforming Growth Factor β1 (TGF-β1) Suppresses Growth of B-cell Lymphoma Cells by p14ARF-dependent Regulation of Mutant p53

2012 ◽  
Vol 287 (27) ◽  
pp. 23184-23195 ◽  
Author(s):  
Gang Chen ◽  
Paritosh Ghosh ◽  
Thomas O'Farrell ◽  
Rachel Munk ◽  
Louis J. Rezanka ◽  
...  
Keyword(s):  
Growth Factor ◽  
B Cell ◽  
Transforming Growth Factor ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Transforming Growth Factor Β1 ◽  
Mutant P53 ◽  
Lymphoma Cells ◽  
Tgf Β1

Specificity protein 1 and Smad-dependent regulation of human heme oxygenase-1 gene by transforming growth factor-β1 in renal epithelial cells

2007 ◽  
Vol 293 (3) ◽  
pp. F885-F894 ◽  
Author(s):  
Amie Traylor ◽  
Thomas Hock ◽  
Nathalie Hill-Kapturczak
Keyword(s):  
Growth Factor ◽  
Heme Oxygenase ◽  
Transforming Growth Factor ◽  
Tissue Injury ◽  
Transforming Growth Factor Β1 ◽  
Molecular Regulation ◽  
Heme Oxygenase 1 ◽  
Specificity Protein 1 ◽  
Specificity Protein ◽  
Tgf Β1

Excess transforming growth factor-β1 (TGF-β1) in the kidney leads to increased cell proliferation and deposition of extracellular matrix, resulting in progressive kidney fibrosis. TGF-β1, however, stabilizes and attenuates tissue injury through the activation of cytoprotective proteins, including heme oxygenase-1 (HO-1). HO-1 catabolizes pro-oxidant heme into substances with anti-oxidant, anti-apoptotic, anti-fibrogenic, vasodilatory and immune modulatory properties. Little is known regarding the molecular regulation of human HO-1 induction by TGF-β1 except that it is dependent on de novo RNA synthesis and requires a group of structurally related proteins called Smads. It is not known whether other DNA binding proteins are required to initiate transcription of HO-1 and, furthermore, the promoter region(s) involved in TGF-β1-mediated induction of HO-1 has not been identified. The purpose of this study was to further delineate the molecular regulation of HO-1 by TGF-β1 in human renal proximal tubular cells. Actinomycin D and nuclear run-on studies demonstrate that TGF-β1 augments HO-1 expression by increased gene transcription and does not involve increased mRNA stability. Using transient transfection, mithramycin A, small interfering RNA, electrophoretic mobility shift assays, and decoy oligonucleotide experiments, a TGF-β1-responsive region is identified between 9.1 and 9.4 kb of the human HO-1 promoter. This ∼280-bp TGF-β1-responsive region contains a putative Smad binding element and specificity protein 1 binding sites, both of which are required for human HO-1 induction by TGF-β1.

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