Transforming growth factor beta 1orTGF-β1 is a polypeptide member of the transforming growth factor beta superfamilyofcytokines. It is a secreted protein that performs many cellular functions, including the control of cell growth, cell proliferation, cell differentiation, and apoptosis. In humans, TGF-β1 is encoded by the TGFB1 gene.[5][6]
TGF-β is a multifunctional set of peptides that controls proliferation, differentiation, and other functions in many cell types. TGF-β acts synergistically with transforming growth factor-alpha (TGF-α) in inducing transformation. It also acts as a negative autocrine growth factor. Dysregulation of TGF-β activation and signaling may result in apoptosis. Many cells synthesize TGF-β and almost all of them have specific receptors for this peptide. TGF-β1, TGF-β2, and TGF-β3 all function through the same receptor signaling systems.[7]
TGF-β1 was first identified in human platelets as a protein with a molecular mass of 25 kilodaltons with a potential role in wound healing.[8][9] It was later characterized as a large protein precursor (containing 390 amino acids) that was proteolytically processed to produce a mature peptide of 112 amino acids.[10]
TGF-β1 plays an important role in controlling the immune system, and shows different activities on different types of cell, or cells at different developmental stages. Most immune cells (orleukocytes) secrete TGF-β1.[11]
Some T cells (e.g. regulatory T cells) release TGF-β1 to inhibit the actions of other T cells. Specifically, TGF-β1 prevents the interleukin(IL)-1- & interleukin-2-dependent proliferation in activated T cells,[12][13] as well as the activation of quiescent helper T cells and cytotoxic T cells.[14][15] Similarly, TGF-β1 can inhibit the secretion and activity of many other cytokines including interferon-γ, tumor necrosis factor-alpha (TNF-α), and various interleukins. It can also decrease the expression levels of cytokine receptors, such as the IL-2 receptor to down-regulate the activity of immune cells. However, TGF-β1 can also increase the expression of certain cytokines in T cells and promote their proliferation,[16] particularly if the cells are immature.[11]
TGF-β1 has similar effects on B cells that also vary according to the differentiation state of the cell. It inhibits proliferation, stimulates apoptosis of B cells,[17] and controls the expression of antibody, transferrin and MHC class II proteins on immature and mature B cells.[11][17]
The effects of TGF-β1 on macrophages and monocytes are predominantly suppressive; this cytokine can inhibit the proliferation of these cells and prevent their production of reactive oxygen (e.g. superoxide (O2−)) and nitrogen (e.g. nitric oxide (NO)) intermediates. However, as with other cell types, TGF-β1 can also have the opposite effect on cells of myeloid origin. For example, TGF-β1 acts as a chemoattractant, directing an immune response to certain pathogens. Likewise, macrophages and monocytes respond to low levels of TGF-β1 in a chemotactic manner. Furthermore, the expression of monocytic cytokines (such as interleukin(IL)-1α, IL-1β, and TNF-α),[15] and macrophage's phagocytic can be increased by the action of TGF-β1.[11]
TGF-β1 reduces the efficacy of the MHC IIinastrocytes and dendritic cells, which in turn decreases the activation of appropriate helper T cell populations.[18][19]
TGF beta 1 has been shown to interact with:
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