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Tumor necrosis factor (TNF), formerly known as TNF-α, is a chemical messenger produced by the immune system that induces inflammation. [5] TNF is produced primarily by activated macrophages , and induces inflammation by binding to its receptors on other cells. [ 6 ]
Tumor necrosis factors (and other cytokines) are produced by cells of the innate immune system during local injury and infection. These contribute to initiating a cascade of mediator release, and recruiting inflammatory cells to the site of infection to contain infection, referred to as "innate immunity.".
The tumor necrosis factor (TNF) superfamily is a protein superfamily of type II transmembrane proteins containing TNF homology domain and forming trimers. Members of this superfamily can be released from the cell membrane by extracellular proteolytic cleavage and function as a cytokine .
Peripheral immune cells are called to the site of injury via these cytokines and may now migrate across the compromised blood brain barrier into the brain. Common cytokines produced in response to brain injury include: interleukin-6 (IL-6), which is produced during astrogliosis, and interleukin-1 beta (IL-1β) and tumor necrosis factor alpha ...
While IL-1β is released by monocytes and macrophages, it is also present in nociceptive DRG neurons. IL-6 plays a role in neuronal reaction to an injury. TNF-α is a well known proinflammatory cytokine present in neurons and the glia. TNF-α is often involved in different signaling pathways to regulate apoptosis in the cells.
The tumor necrosis factor receptor superfamily (TNFRSF) is a protein superfamily of cytokine receptors characterized by the ability to bind tumor necrosis factors (TNFs) via an extracellular cysteine-rich domain. [2] [3] With the exception of nerve growth factor (NGF), all TNFs are homologous to the archetypal TNF-alpha. [4]
[94] [95] Inflammatory compounds, such as tumor necrosis factor (TNF)-alpha released by the macrophages activate the gene switch nuclear factor-kappa B. NF-κB then enters the nucleus of a tumor cell and turns on production of proteins that stop apoptosis and promote cell proliferation and inflammation. [ 96 ]
Microglia are a type of glial cell located throughout the brain and spinal cord of the central nervous system (CNS). [1] Microglia account for about 10–15% of cells found within the brain. [2] As the resident macrophage cells, they act as the first and main form of active immune defense in the CNS. [3]