TNF causes apoptotic cell death, cellular proliferation, differentiation, inflammation, tumorigenesis and viral replication, TNF is also involved in lipid metabolism, and coagulation. TNF's primary role is in the regulation of immune cells.
Dysregulation and, in particular, overproduction of TNF have been implicated in a variety of human diseases- autoimmune diseases, insulin resistance, and cancer.
The TNF-alpha is purified by standard chromatographic techniques.
TNF-alpha Human was lyophilized from a concentrated 1mg/ml solution containing 20mM PB, pH-7.2, and 100mM NaCl.
Lyophilized Tumor Necrosis Factor-a although stable at room temperature for 3 weeks, should be stored desiccated below -18°C. Upon reconstitution TNF-a should be stored at 4°C between 2-7 days and for future use below -18°C.
For long term storage it is recommended to add a carrier protein (0.1% HSA or BSA).
Please prevent freeze-thaw cycles.
(a) Analysis by RP-HPLC.
(b) Analysis by SDS-PAGE.
Amino acid sequence
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Tnf-alpha stands for tumour necrosis factor, and it is a cell signalling protein found in the human body. Part of systemic inflammation, it is just one of the cytokines that trigger the acute phase reaction. These proteins with plasma concentrations decrease or increase in response to inflammation.
Tnf-alpha is typically produced by macrophages being activated. A type of white blood cell, these calls digest cellular debris and cancer cells or really any type of protein that doesn’t have surface healthy body cells. However, it is possible that it can be produced through other cell types includes NK cells, eosinophils, neurons, lymphocytes as well as various others.
The main function of Tnf-alpha is to regulate immune cells in the body. Because it is endogenous pyrogen, the protein is able to induce everything from inflammation to apoptotic cell death. Furthermore, the protein can also prevent tumorigenesis and respond to sepsis. It does this through IL1 and IL6 producing cells. Various human diseases have been associated with or connected to the dysregulation of Tnf production. Some of these diseases include, Alzheimer’s, cancer, depression and IBD. Furthermore, Tnf can be created ectopically, in the presence of a malignant parathyroid hormone, particularly in cancers where there is typically an increased level of production.
TNF has various actions on different organ systems. For instance, on the liver, it stimulates the acute phase response and this leads to additional development of C-reactive protein as well as other mediators. Furthermore, it also provides insulin resistance and it does this by triggering serine-phosphorylation of IRS-1. This negatively impacts insulin signalling.
In the hypothalamus, TNF-alpha has been shown to both suppress appetite and trigger a fever.
Tnf-alpha has been studied and shown to interact with TNFRSF1A. This is a ubiquitous membrane receptor that can bind tumor necrosis factor alpha. This can also function as a regulator of levels of inflammation.
Studies have also shown interactions between IL-5 and Tnf-a genotypes that are associated with bacteremia present in patients with myeloma. The transplantation of stem cells impacts patients level of risk to infections due to changes to their immune system. Increased levels of TNF-a impact the immune response and an interaction analysis has shown that there was an interaction between the two. Further research has also shown that interactions between IL-10 and TNF-A are able to regulate prostaglandin E2 production and lipopolysaccharide-stimulated human choriodecidual cytokine.
TNF is primarily produced as a 233-amino acid long type II transmembrane protein. It is arranged in stable homotetramers. From this, the homotrimeric cytokine is released by the TNF alpha converting enzyme. This tends to disassociate at certain concentrations, usually those below the nanomolar range, making them lose their bioactivity. The human form of TNF-alpha is a triangle shape and is roughly 17-kd in weight.
Research is ongoing exploring the full impact of TNF-alpha on the human body including its effect on various psychological and physical conditions. Thus far, anti-TNF therapy has provided only a low impact as a form of cancer therapy.