Tumor necrosis factor alpha

TNF-αTNF-alphaTNFαtumor necrosis factortumor necrosis factor-alphaTNF alphatumor necrosis factor-αtumor necrosis factor αTNFTNFA
Tumor necrosis factor (TNF, cachexin, or cachectin; once named as tumor necrosis factor alpha or TNFα) is a cell signaling protein (cytokine) involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction.wikipedia
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Cachexia

wasting syndromecachecticcancer cachexia
TNF, being an endogenous pyrogen, is able to induce fever, apoptotic cell death, cachexia, inflammation and to inhibit tumorigenesis and viral replication and respond to sepsis via IL1- & IL6-producing cells. In 1985, Bruce A. Beutler and Anthony Cerami discovered that cachectin (a hormone which induces cachexia) was actually TNF.
Inflammatory cytokines appear to play a central role including TNF-alpha (which is also nicknamed 'cachexin' or 'cachectin'), interferon gamma and interleukin 6.

Lloyd J. Old

Lloyd Old
Subsequently, in 1975 Lloyd J. Old from Memorial Sloan-Kettering Cancer Center, New York, reported another cytotoxic factor produced by macrophages and named it tumor necrosis factor (TNF).
In earlier work, he and his colleagues introduced Bacillus Calmette-Guérin (BCG) to tumor immunotherapy; discovered the first link between the major histocompatibility complex (MHC) and disease (leukemia); found the unexpected association between Epstein-Barr virus (EBV) and nasopharyngeal carcinoma; discovered Tumor necrosis factors (TNF); defined the concept of cell-surface differentiation antigens with the discovery of TL, Lyt (CD8), and a range of other mouse antigenic systems; discovered p53, independently with two other groups; and identified the tumor immunogenicity of heat shock proteins.

Mast cell

mast cellsanaphylactic degranulationMast cell disease
It is produced chiefly by activated macrophages, although it can be produced by many other cell types such as CD4+ lymphocytes, NK cells, neutrophils, mast cells, eosinophils, and neurons. TNF was thought to be produced primarily by macrophages, but it is produced also by a broad variety of cell types including lymphoid cells, mast cells, endothelial cells, cardiac myocytes, adipose tissue, fibroblasts, and neurons.

Psoriasis

plaque psoriasispsoriasis vulgarispsoriatic
Dysregulation of TNF production has been implicated in a variety of human diseases including Alzheimer's disease, cancer, major depression, psoriasis and inflammatory bowel disease (IBD).
These immune cells move from the dermis to the epidermis and secrete inflammatory chemical signals (cytokines) such as interleukin-36γ, tumor necrosis factor-α, interleukin-1β, interleukin-6, and interleukin-22.

Eosinophil

eosinophilseosinophil granulocyteEosino
It is produced chiefly by activated macrophages, although it can be produced by many other cell types such as CD4+ lymphocytes, NK cells, neutrophils, mast cells, eosinophils, and neurons.

ADAM17

ADAM 17 MetallopeptidaseCD156bTNF- alpha converting enzyme
From this membrane-integrated form the soluble homotrimeric cytokine (sTNF) is released via proteolytic cleavage by the metalloprotease TNF alpha converting enzyme (TACE, also called ADAM17).
ADAM17 is understood to be involved in the processing of tumor necrosis factor alpha (TNF-α) at the surface of the cell, and from within the intracellular membranes of the trans-Golgi network.

TNF receptor superfamily

tumor necrosis factor receptordeath receptorTNFR
TNF can bind two receptors, TNFR1 (TNF receptor type 1; CD120a; p55/60) and TNFR2 (TNF receptor type 2; CD120b; p75/80).
With the exception of nerve growth factor (NGF), all TNFs are homologous to the archetypal TNF-alpha.

Tumor necrosis factor receptor 2

TNFR2TNFRSF1Btumor necrosis factor receptor superfamily, member 1B
TNF can bind two receptors, TNFR1 (TNF receptor type 1; CD120a; p55/60) and TNFR2 (TNF receptor type 2; CD120b; p75/80).
Tumor necrosis factor receptor 2 (TNFR2), also known as tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) and CD120b, is a membrane receptor that binds tumor necrosis factor-alpha (TNFα).

Sepsis

septicaemiablood poisoningseptic
TNF, being an endogenous pyrogen, is able to induce fever, apoptotic cell death, cachexia, inflammation and to inhibit tumorigenesis and viral replication and respond to sepsis via IL1- & IL6-producing cells.
Cytokines such as tumor necrosis factor, interleukin 1, and interleukin 6 may activate procoagulation factors in the cells lining blood vessels, leading to endothelial damage.

Bruce Beutler

Bruce A. Beutler
In 1985, Bruce A. Beutler and Anthony Cerami discovered that cachectin (a hormone which induces cachexia) was actually TNF.
He was the first to isolate mouse tumor necrosis factor-alpha (TNF), and to demonstrate the inflammatory potential of this cytokine, proving its important role in endotoxin-induced shock.

Fever

pyrexiafebrileague
TNF, being an endogenous pyrogen, is able to induce fever, apoptotic cell death, cachexia, inflammation and to inhibit tumorigenesis and viral replication and respond to sepsis via IL1- & IL6-producing cells.
Tumor necrosis factor-α also acts as a pyrogen.

Immune system

immuneimmune responseimmune function
The theory of an anti-tumoral response of the immune system in vivo was recognized by the physician William B. Coley.
Complex feedback loops involving cytokines, such as interleukin-1 and tumor necrosis factor-α produced in response to infection, appear to also play a role in the regulation of non-rapid eye movement (REM) sleep.

Macrophage

macrophagesM2 macrophagesTissue macrophages
Subsequently, in 1975 Lloyd J. Old from Memorial Sloan-Kettering Cancer Center, New York, reported another cytotoxic factor produced by macrophages and named it tumor necrosis factor (TNF). It is produced chiefly by activated macrophages, although it can be produced by many other cell types such as CD4+ lymphocytes, NK cells, neutrophils, mast cells, eosinophils, and neurons. TNF was thought to be produced primarily by macrophages, but it is produced also by a broad variety of cell types including lymphoid cells, mast cells, endothelial cells, cardiac myocytes, adipose tissue, fibroblasts, and neurons.
Inflammatory compounds such as tumor necrosis factor (TNF)-alpha released by the macrophages activate the gene switch nuclear factor-kappa B.

Septic shock

septicshockshock, septic
Kevin J. Tracey and Cerami discovered the key mediator role of TNF in lethal septic shock, and identified the therapeutic effects of monoclonal anti-TNF antibodies.
It also results in profound activation of mononuclear cells and the production of potent effector cytokines such as IL-1, IL-6, and TNF-α.

Natural killer cell

NK cellsnatural killer cellsNK cell
It is produced chiefly by activated macrophages, although it can be produced by many other cell types such as CD4+ lymphocytes, NK cells, neutrophils, mast cells, eosinophils, and neurons.
Some important cytokines they secrete include TNF-α, IL-10, IFN-γ, and TGF-β, among others.

Cytokine

cytokineschemical signalscytokine-
Tumor necrosis factor (TNF, cachexin, or cachectin; once named as tumor necrosis factor alpha or TNFα) is a cell signaling protein (cytokine) involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction.
Virtually all nucleated cells, but especially endo/epithelial cells and resident macrophages (many near the interface with the external environment) are potent producers of IL-1, IL-6, and TNF-α.

NF-κB

NF-kBNF-kappaBNFκB
More recently, research in the Laboratory of Mark Mattson has shown that TNF can prevent the death/apoptosis of neurons by a mechanism involving activation of the transcription factor NF-kappaB which induces the expression of Mn-SOD and Bcl-2.
Known inducers of NF-κB activity are highly variable and include reactive oxygen species (ROS), tumor necrosis factor alpha (TNFα), interleukin 1-beta (IL-1β), bacterial lipopolysaccharides (LPS), isoproterenol, cocaine, and ionizing radiation.

Anthony Cerami

In 1985, Bruce A. Beutler and Anthony Cerami discovered that cachectin (a hormone which induces cachexia) was actually TNF.
He developed and validated a measurement of glycated hemoglobin to monitor control of blood sugar in people with diabetes, and a paper he published in 1985 using polyclonal antibodies against tumour necrosis factor-alpha was important in the field of immunology for demonstrating that TNF-alpha causes disease and blocking it could be a treatment.

Lymphotoxin

TNF betaTNF-βtumor necrosis factor β
In 1968, Gale A Granger from the University of California, Irvine, reported a cytotoxic factor produced by lymphocytes and named it lymphotoxin (LT).

Alzheimer's disease

AlzheimerAlzheimer’s diseaseAlzheimer disease
Dysregulation of TNF production has been implicated in a variety of human diseases including Alzheimer's disease, cancer, major depression, psoriasis and inflammatory bowel disease (IBD).
A TNFα receptor-blocking fusion protein, etanercept has showed encouraging results.

Kevin J. Tracey

Kevin J. Tracey and Cerami discovered the key mediator role of TNF in lethal septic shock, and identified the therapeutic effects of monoclonal anti-TNF antibodies.
In the early 1980s, Tracey and colleagues described the inflammatory activity of TNF-α and other cytokines, which ultimately led to the discovery and development of disease-modifying antirheumatic drugs for arthritis.

Adipose tissue

adiposebody fatfat
TNF was thought to be produced primarily by macrophages, but it is produced also by a broad variety of cell types including lymphoid cells, mast cells, endothelial cells, cardiac myocytes, adipose tissue, fibroblasts, and neurons.
Far from being hormonally inert, adipose tissue has, in recent years, been recognized as a major endocrine organ, as it produces hormones such as leptin, estrogen, resistin, and cytokine (especially TNFα).

Apoptosis

apoptoticprogrammed cell deathcell death
TNF, being an endogenous pyrogen, is able to induce fever, apoptotic cell death, cachexia, inflammation and to inhibit tumorigenesis and viral replication and respond to sepsis via IL1- & IL6-producing cells. More recently, research in the Laboratory of Mark Mattson has shown that TNF can prevent the death/apoptosis of neurons by a mechanism involving activation of the transcription factor NF-kappaB which induces the expression of Mn-SOD and Bcl-2.
Two theories of the direct initiation of apoptotic mechanisms in mammals have been suggested: the TNF-induced (tumor necrosis factor) model and the Fas-Fas ligand-mediated model, both involving receptors of the TNF receptor (TNFR) family coupled to extrinsic signals.

Inflammation

inflammatoryinflammatory responseinflamed
Tumor necrosis factor (TNF, cachexin, or cachectin; once named as tumor necrosis factor alpha or TNFα) is a cell signaling protein (cytokine) involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction.
Inflammatory mediators that contribute to neoplasia include prostaglandins, inflammatory cytokines such as IL-1β, TNF-α, IL-6 and IL-15 and chemokines such as IL-8 and GRO-alpha.

Interleukin 6

IL-6interleukin-6IL6
TNF, being an endogenous pyrogen, is able to induce fever, apoptotic cell death, cachexia, inflammation and to inhibit tumorigenesis and viral replication and respond to sepsis via IL1- & IL6-producing cells.
IL-6's role as an anti-inflammatory myokine is mediated through its inhibitory effects on TNF-alpha and IL-1, and activation of IL-1ra and IL-10.