How does TGF-β-Neutralizing Antibody 1D11 work?5 answersThe TGF-β-neutralizing antibody 1D11 works by targeting the TGF-β signaling pathway to exert its effects in various conditions. In metastatic breast cancer, 1D11 enhances the CD8+ T-cell-mediated antitumor immune response, increases infiltration of natural killer cells and T cells at metastatic sites, and enhances expression of cytotoxic effectors on CD8+ T cells. In osteogenesis imperfecta, 1D11 treatment increases trabecular bone volume and strength, suppresses serum biomarkers of bone turnover, and affects osteoblast and osteoclast numbers. In cancer therapy, specifically in colon cancer and melanoma models, blocking TGF-β1 with 1D11 enhances the efficacy of immunotherapies by increasing infiltration of activated CD8 T cells and delaying tumor progression through a tumor-intrinsic effect. Additionally, in T. cruzi infection, 1D11 reduces cardiomyocyte invasion and parasite load, improving cardiac performance and reducing fibrosis.
What is a TGF-B ?4 answersTransforming growth factor-β (TGF-β) is a multifunctional cytokine involved in cancer progression, immune regulation, and tissue homeostasis. In cancer, TGF-β exhibits dual roles, acting as a tumor suppressor in early stages by inducing apoptosis and cell cycle arrest, while promoting tumor growth, invasion, and metastasis in advanced stages. TGF-β also plays a crucial role in immune suppression within the tumor microenvironment, limiting T cell activation and promoting resistance to immune checkpoint inhibitors. Moreover, TGF-β can modulate the behavior of pericytes in glioblastoma, leading to blood-brain barrier disruption. Additionally, TGF-β-producing B cells have been implicated in regulating immune responses in cancer, autoimmune disorders, and inflammatory diseases. Overall, TGF-β is a key player in various physiological and pathological processes, making it a potential target for therapeutic interventions.
How TGF beta 1 protein purified from e.coli?4 answersTransforming growth factor beta 1 (TGF-β1) protein can be purified from Escherichia coli (E. coli) using various methods. One approach involves the use of fusion tags to increase solubility and facilitate purification. For example, the fusion of TGF-β1 with thioredoxin (Trx) or superfolder GFP (sfGFP) has been successful in producing soluble forms of the protein. After expression in E. coli, the fusion protein is typically found in insoluble form as inclusion bodies. These inclusion bodies can be solubilized and refolded using redox systems such as glutathione or glutathione redox-coupled systems. The fusion protein can then be purified using affinity chromatography, such as Ni-NTA agarose, to separate the carrier protein from the target protein. Additional purification steps, such as cation-exchange chromatography, can be employed to separate monomeric molecules from noncovalently bound oligomers. The purified TGF-β1 protein can be confirmed for its structure and biological activity using techniques like circular dichroism analysis and bioassays.
What is the role of TGF-β in NET formation and function?4 answersTGF-β is a potent immunosuppressive cytokine that affects the function of NK cells. It can alter the expression of effector molecules, chemokine receptors, and activate the conversion of NK cells to less cytolytic ILC1s. TGF-β signaling in lymphatic endothelial cells maintains the structure of lymphatic vessels and promotes tumor lymphatic metastasis. TGF-β is involved in the formation and maintenance of microtubes (MTs) in glioblastomas (GBMs), promoting enhanced MT formation and communication via Calcium signaling. TGF-β modulates gene expression by affecting transcriptional activation and mRNA turnover rate, potentially leading to changes in the proteome and cellular metabolism.
Dose IL-1β and transforming growth factor-beta (TGF-β) impact to influence early embryo development?5 answersIL-1β and TGF-β have been shown to impact early embryo development. IL-1β can modulate the growth of bovine embryos at early stages, with its effect depending on embryo density. It has been found to increase development to the blastocyst stage when embryos are cultured at high density, but may decrease or have no effect on development when cultured at low density. On the other hand, TGF-β1 has been shown to have an early action on bovine embryos, with exposure to exogenous TGF-β1 leading to an increase in the relative abundance of pluripotency and DNA methylation genes in the embryos. These findings suggest that both IL-1β and TGF-β can influence early embryo development, with IL-1β's effect depending on embryo density and TGF-β1's effect involving the modulation of gene expression.
What is the role of TGF-beta pathway in synovial degeneration in knee osteoarthritis?5 answersThe TGF-beta pathway plays a critical role in synovial degeneration in knee osteoarthritis (OA). Excessive activation of TGF-β leads to uncoupled bone remodeling, increased angiogenesis, and fibrosis in the subchondral bone, which contributes to the degeneration of articular cartilage. TGF-β also serves as a pro-inflammatory factor in the synovium, augmenting the secretion of inflammatory factors by immune cells. Inhibition of the TGF-β1 signaling cascade has been shown to improve the treatment of OA in the knee joint. Additionally, TGF-β/SMAD pathway has been found to play a critical role in articular chondrocytes, mesenchymal progenitor cells of subchondral bone, and synovial lining cells during OA development. The conflicting roles of TGF-β1 signaling in the development of OA are still under investigation.