Fundamentals of Tumor Necrosis Factor & Epidermal Growth Factor

Tumor Necrosis Factor

Tumor necrosis factor-alpha (TNFα), a human cytokine, is associated with systemic inflammation and is an integral component of the acute phase reaction.  This soluble homotrimeric cytokine is primarily produced by activated macrophages but can be produced by other cell types such as natural killer cells, mast cells, T helper cells, eosinophils, and neutrophils. As a result of its production by monocytes and macrophages, endotoxins as well as bacterially derived products can induce its secretion. Tumor necrosis factor-alpha (TNFα), a cellular signaling protein, is involved in systemic inflammation and is part of the acute phase reaction to tissue injury. TNFα is produced primarily by activated macrophages, although it can be produced by many other cell types such as NK cells, T lymphocytes, mast cells, eosinophils, and neutrophils. Its primary role is in regulating immune cells.

Tumor necrosis factor alpha (TNFα) is a human cytokine produced primarily by macrophages that, when released in high levels, is associated with systemic inflammation. In addition to its role in inflammation, TNFα helps in cellular homeostasis and survival by downregulating the production of proinflammatory mediators and upregulating anti-inflammatory mediators. TNFα also has significant roles in growth and maturation of cells during embryonic development, as well as in apoptosis or cell death.

Tumor necrosis factor (TNF, tumor necrosis factor alpha, TNFα) is a cell signaling protein (cytokine) involved in systemic inflammation. It is produced chiefly by activated macrophages and can bind to TNF receptor 1 (TNFr1), which is expressed by almost all cells in the body, and TNF receptor 2 (TNFr2), which is mostly expressed by cells of the immune system. The primary role of TNF is in the regulation of immune cells.  Dysregulation of TNF has been implicated as a factor in many human diseases, primarily diseases that involve an excessive inflammatory response such as rheumatoid arthritis and Crohn’s disease, but also including diseases not generally considered inflammatory such as Alzheimer’s disease and cancer.

Epidermal growth factor (EGF), a founding member of the EGF-family of proteins is a 6 kilodalton protein belonging to the EGF-protein family. EGF binds to the epidermal growth factor receptor (EGFR) and stimulates cell growth and differentiation . In humans, this protein is made of 53 amino acid residues and its tertiary structure is held together by 3 intramolecular disulfide bonds. Researchers first identified EGF in human urine and mice submaxillary glands as a secreted protein. Since then, EGF has been found in tears, saliva, milk, plasma, and tissues, including the parotid gland and submandibular gland-urogastrone or its trade name Heberprot-P. Epidermal growth factor (EGF) was the first growth factor to be discovered.

EGF is a simple-chain polypeptide containing 53 amino acids that has been extensively studied. EGF has been shown to have mitogenic activity in target epithelial cells, fibroblasts, and other cells. The growth-promoting effects of EGF in skin have been demonstrated both in the laboratory and clinic, with the involvement of dysregulated EGFR expression in malignant progression. We investigate the molecular mechanisms regulated by EGF signaling through EGFR.

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