Tumor Necrosis Factor

About Tumor Necrosis Factor:

Tumor necrosis factor alpha is a protein that’s part of the cytokine family. Cytokines are a rather diverse category of proteins that are essential when it comes to cell signalling. This particular cytokine - TNF Alpha - is one of the cell signalling proteins that form the acute phase reaction.

Mechanism/Interactions
TNF Alpha is primarily created by the activation of macrophages. These are a grouping of white blood cells that serve to ingest anything that doesn’t contain typical health body cell proteins. However, TNF Alpha can also be produced by multiple other cell types in the body. This includes mast cells, neurons, CD4+ lymphocytes, NK cells, eosinophils, and even neutrophils. This protein has also been discovered to interact with TNFR1, or tumour necrosis factor receptor 1. In doing so, it can bind this receptor with TNFR2. TNFR1 is most commonly abundant in the majority of tissue cells in the body. TNF can activate this receptor in both its membrane-bound and soluble forms. On the other hand, TNFR2 is commonly present in the immune system, and will only be activated by the membrane-bound form or TNF. These two receptors work together to send signals throughout cells.

Function
The main function of TNF Alpha is to regulate the immune cells. It has the ability to induce a fever, speed up cell death, create inflammation, and so much more. TNF is released in vast quantities when bacterial products such as lipopolysaccharide and interleukin-1 are present.
It works in many different ways with different parts of the body. More often than not, TNF will work alongside IL-1 and IL-6. It stimulates the acute phase response on the liver, which can lead to a growing amount of C-reactive protein in this organ. Furthermore, TNF functions to bring about insulin resistance, which prevents blood sugar levels from properly decreasing.
When concentration levels of TNF are increased, it leads to inflammation signs such as swelling, pain, and redness. Abnormally high levels of TNF have also been linked to a wasting syndrome that causes the body to drastically lose weight at an unhealthy rate. This is often common in cancer patients.
Therefore, many inflammatory diseases have been treated by using a TNF inhibitor. This prevents TNF Alpha from functioning properly, reducing the signs of inflammation.

Structure
TNF Alpha is largely arranged in stable homotrimers. It is a 233-amino acid long protein, of the type II transmembrane family. sTNF - which is the soluble homotrimeric cytokine - is released from TNF when it is in the membrane-bound form. When concentration reaches a nanomolar level or below, the soluble TNF begins to lose some of its bioactivity.
When secreted, the human form of TNF Alpha become triangular in its shape, almost resembling a pyramid. While in this form, TNF Alpha ways approximately 17-kD. The secreted form, along with the membrane-bound form, are both incredibly active on a biological scale. Both forms of TNF do have certain functions that are controversial with one another. However, they also have various biological activities that overlap and interlink with one another too.
This protein is mainly created and induced by cells in the epithelium right on barrier surfaces.