TGF beta 1
name=transforming growth factor, beta 1
Transforming growth factor beta 1 or TGF-β1 is a polypeptide member of the
transforming growth factor beta superfamilyof cytokines. It is a secreted protein that performs many cellular functions, including the control of cell growth, cell proliferation, cell differentiationand apoptosis.
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. [cite journal |author=Assoian R, Komoriya A, Meyers C, Miller D, Sporn M |title=Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization |journal=J Biol Chem |volume=258 |issue=11 |pages=7155–60 |year=1983 |pmid=6602130] 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. [cite journal |author=Derynck R, Jarrett J, Chen E, Eaton D, Bell J, Assoian R, Roberts A, Sporn M, Goeddel D |title=Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells |journal=Nature |volume=316 |issue=6030 |pages=701–5 |year=1985 |pmid=3861940 |doi=10.1038/316701a0]
TGF-β1 plays an important role in controlling the
immune system, and shows diiferent activities on different types of cell, or cells at different developmental stages. Most immune cells (or leukocytes) secrete TGF-β1.cite journal |author=Letterio J, Roberts A |title=Regulation of immune responses by TGF-beta |journal=Annu Rev Immunol |volume=16 |issue= |pages=137–61 |year= |pmid=9597127 |doi=10.1146/annurev.immunol.16.1.137]
TGF-β1 and T cells
T cells (e.g. regulatory T cells) release TGF-β1 to inhibit the actions of other T cells. Interleukin 1- and interleukin 2-dependent proliferation of activated T cells, [cite journal |author=Wahl S, Hunt D, Wong H, Dougherty S, McCartney-Francis N, Wahl L, Ellingsworth L, Schmidt J, Hall G, Roberts A |title=Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation |journal=J Immunol |volume=140 |issue=9 |pages=3026–32 |year=1988 |pmid=3129508] [cite journal |author=Tiemessen M, Kunzmann S, Schmidt-Weber C, Garssen J, Bruijnzeel-Koomen C, Knol E, van Hoffen E |title=Transforming growth factor-beta inhibits human antigen-specific CD4+ T cell proliferation without modulating the cytokine response |journal=Int Immunol |volume=15 |issue=12 |pages=1495–504 |year=2003 |pmid=14645158 |doi=10.1093/intimm/dxg147] and the activation of quiescent helper T cells and cytotoxic T cells is prevented by the activity of TGF-β1. [cite journal |author=Gilbert K, Thoman M, Bauche K, Pham T, Weigle W |title=Transforming growth factor-beta 1 induces antigen-specific unresponsiveness in naive T cells |journal=Immunol Invest |volume=26 |issue=4 |pages=459–72 |year=1997 |pmid=9246566] cite journal |author=Wahl S, Wen J, Moutsopoulos N |title=TGF-beta: a mobile purveyor of immune privilege |journal=Immunol Rev |volume=213 |issue= |pages=213–27 |year=2006 |pmid=16972906 |doi=10.1111/j.1600-065X.2006.00437.x] 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 receptorto 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, particularly if the cells are immature. [cite journal |author=Letterio J, Roberts A |title=Regulation of immune responses by TGF-beta |journal=Annu Rev Immunol |volume=16 |issue= |pages=137–61 |year=1998 |pmid=9597127 |doi=10.1146/annurev.immunol.16.1.137]
TGF-β1 and B cells
TGF-β1 has similar effects on
B cells that also vary according to the differentiation state of the cell. It inhibits proliferation and apoptosisof B cells,cite journal |author=Lebman D, Edmiston J |title=The role of TGF-beta in growth, differentiation, and maturation of B lymphocytes |journal=Microbes Infect |volume=1 |issue=15 |pages=1297–304 |year=1999 |pmid=10611758 |doi=10.1016/S1286-4579(99)00254-3] and plays a role in controlling the expression of antibody, transferrinand MHC class IIproteins on immature and mature B cells.
TGF-β1 and myeloid cells
The effects of TGF-β1 on
macrophages and monocytes is 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 some pathogens; macrophages and monocytes respond to low levels of TGF-β1 in a chemotactic manner. Furthermore, the expression of monocytic cytokines (including interleukin-1(IL-1)-alpha, IL-1-beta, and TNF-α), and phagocytic killing by macrophages can be increased by the action of TGF-β1.
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