Search results for "Transforming growth factor"

Asthmatic changes in mice lacking T-bet are mediated by IL-13

2005

Mice with a targeted deletion of the T-bet gene exhibit spontaneous airway hyperresponsiveness (AHR), airway inflammation, enhanced recovery of T(h)2 cytokines from bronchoalveolar lavage fluid, sub-epithelial collagen deposition and myofibroblast transformation. Here we analyze the mechanisms responsible for the chronic airway remodeling observed in these mice. CD4+ T cells isolated from the lung of T-bet-deficient mice were spontaneously activated CD44(high)CD69(high) memory T cells, with a typical T(h)2 cytokine profile. Neutralization of IL-13 but not IL-4 resulted in amelioration of AHR in airways of mice lacking T-bet. IL-13 blockade also led to reduced eosinophilia and decreased vime…

Potential involvement of IL-9 and Th9 cells in the pathogenesis of rheumatoid arthritis

2015

Objective IL-9 has been shown to be upregulated before the clinical onset of articular disease in RA. The exact role of IL-9 and Th9 cells in RA, however, has not yet been adequately studied. The aim of this study was to evaluate the expression of IL-9 and IL-9-expressing cells in RA patients. Methods IL-9, IL-9R, PU.1, IL-9, thymic stromal lymphopoietin (TSLP), IL-4 and TGF-β expression was assessed by real-time-PCR in the synovial tissues of RA and OA patients. IL-9, IL-9R, IL-4, TSLP and TGF-β were also investigated by immunohistochemistry. Peripheral CD4(+) T cell subsets were studied by flow cytometry analysis before and after incubation with citrullinated peptides. Results IL-9 was ov…

Autocrine transforming growth factor- from chronic lymphocytic leukemia-β cells interferes with proliferative T cell signals

1999

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of noncycling B cells in lymphatic and extralymphatic tissues. In the present study we investigated the possible contribution of TGF-beta, as secreted by CLL-B cells, on this low proliferative state. CLL-B cells were shown to express TGF-beta RNA and to release bioactive TGF-beta into culture supernatants. Antibody neutralization of endogenously secreted TGF-beta increased the proliferation of CLL-B cells as cultured in the presence of IL-2 or IL-4 or in direct contact with activated CD4+ T cells. In these culture systems, addition of exogenous TGF-beta downregulated basal and cytokineinduced proliferation of CLL-B cell…

Colorectal cancer-derived small extracellular vesicles induce TGFβ1-mediated epithelial to mesenchymal transition of hepatocytes

2023

Abstract Background Metastatic disease is the major cause of cancer-related deaths. Increasing evidence shows that primary tumor cells can promote metastasis by preparing the local microenvironment of distant organs, inducing the formation of the so-called “pre-metastatic niche”. In recent years, several studies have highlighted that among the tumor-derived molecular components active in pre-metastatic niche formation, small extracellular vesicles (sEVs) play a crucial role. Regarding liver metastasis, the ability of tumor-derived sEVs to affect the activities of non-parenchymal cells such as Kupffer cells and hepatic stellate cells is well described, while the effects on hepatocytes, the m…

Transforming Growth Factor-β–Mediated Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Expression and Apoptosis in Hepatoma Cells Requires Fun…

2008

Abstract Transforming growth factor-β (TGF-β) has been shown to induce apoptotic cell death in normal and transformed hepatocytes. We recently identified tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as an important mediator of TGF-β–induced apoptosis in hepatoma cells. In this study, we have further explored the mechanism by which TGF-β up-regulates TRAIL expression. The 5′-flanking region of the TRAIL gene was isolated and characterized. Deletion mutants of the 5′-untranslated region of the TRAIL gene revealed a region comprising nucleotides −1950 to −1100 responsible for TRAIL induction following treatment with TGF-β. Within this region, we have identified an activator …

Apoptosis and the liver

2000

Regulation of the homeostatic balance between cell proliferation and programmed cell death, apoptosis, is essential for development and maintenance of multicellular organisms. Apoptosis is a genetically and evolutionarily highly conserved process. Analysis of the molecular mechanisms of apoptosis has led to a better understanding of many human diseases. Notably in cancer, but also in infectious or autoimmune disease, a deficiency in apoptosis is one of the key events in pathophysiology. On the other hand, overefficient apoptosis, as observed in fulminant liver failure, may be equally harmful for the organism indicating that a tight regulation of the apoptotic machinery is essential for surv…

Differential inhibition of renal cancer cell invasion mediated by fibronectin, collagen IV and laminin.

2000

Invasion of tumor cells into the extracellular matrix is an essential step in the formation of metastases in renal cancer. Cell adhesion molecules such as beta(1)-integrins, which bind to the RGD sequence (arginine-glycine-asparagine) and CD44 are involved in this process. We examined the invasion of a renal carcinoma cell line (CCF-RC1) into the extracellular matrix compounds fibronectin, collagen IV and laminin and the effect of TGFbeta and IFNgamma on this process. The inhibitory effect of an antibody against the beta(1)-subunit of integrins (CD29), as well as a pentapeptide including the RGD sequence, was also evaluated. A micro-chemotaxis chamber, including a polycarbonate membrane wit…

Transforming growth factor-β1, β2, and β3, urokinase and parathyroid hormone-related peptide expression in 8701-BC breast cancer cells and clones

1993

8701-BC is a recently characterized cell line isolated from a primary ductal infiltrating carcinoma of the breast (d.i.c.), showing some pleomorphism in cell microanatomy at an ultrastructural level. We have obtained different sublines of 8701-BC cells by cloning in soft agar at different concentrations (0.3% and 0.6%), and we have characterized the cloned lines by some morphological and growth parameters. 8701-BC cells and clones have been submitted to analysis by reverse transcriptase-linked polymerase chain reaction to detect mRNAs of various cytokines (transforming growth factor-beta s, tumour necrosis factors, interleukin 1s, interleukin 6, parathyroid hormone-related peptide, gamma in…

The alpha and ßeta in phase II trials hepatocellular carcinoma ‐ A tale of more than radiological response?

2019

2021

Growth and differentiation factor 15 (GDF15) belongs to the transforming growth factor-β (TGF-β) superfamily of proteins. Glial-derived neurotrophic factor (GDNF) family receptor α-like (GFRAL) is an endogenous receptor for GDF15 detected selectively in the brain. GDF15 is not normally expressed in the tissue but is prominently induced by “injury”. Serum levels of GDF15 are also increased by aging and in response to cellular stress and mitochondrial dysfunction. It acts as an inflammatory marker and plays a role in the pathogenesis of cardiovascular diseases, metabolic disorders, and neurodegenerative processes. Identified as a new heart-derived endocrine hormone that regulates body growth,…