Tumor Necrosis Factors (TNF) and Related Peptides
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Introduction
Tumor Necrosis Factor (TNF) is a kind of cytokine which can kill tumor cells directly without obvious toxicity to normal cells. All members of TNF family can express transmembrane proteins of type Ⅱ. It consists of three parts: the intracellular region of the amino terminal, the transmembrane region and the extracellular domain of the carboxyl terminal. TNF was mainly produced by activated macrophages, NK cells and T lymphocytes, which were divided into two types: TNF-α and TNF-β. The TNF produced by macrophages was named TNF-α, and the lymphotoxin (LT) produced by T lymphocytes was named TNF-β. The biological activity of TNF-α accounted for 70% ~ 95% of the total activity of TNF. Therefore, TNF usually refers to TNF-α. The precursor of human TNF-α consists of 233 amino acids, including a signal peptide composed of 76 amino acid residues.
Mechanism of action
Tumor necrosis factor receptor (TNFR) is the receptor of TNF-α. There are two subtypes of TNFR1 and TNFR2. TNFR exists on the surface of many normal cells and tumor cells, and TNF-α binds to target cells by TNFR. The cytolytic activity of TNFR1 cells plays a major role because of the death domain in the intracellular region of TNFR1. When the TNF-α trimer binds to the TNFR1 extracellular domain on the target cell membrane, PA DD binds to the TNFR1 death domain to form a TNFR1/IPA DD complex, which enlists a series of related proteins and triggers different downstream signaling pathways to achieve cytotoxicity. Antivirus, immune regulation and other biological functions.
Application of TNF
TNF-α plays an important role in many diseases, including rheumatoid arthritis, inflammatory bowel disease, septic shock, systemic lupus erythematosus (SLE), vasculitis and type I diabetes. Because of the complexity of the TNF-α related signaling pathway and its multiple roles in different diseases, although there is one-part of the proud success of the current treatment targeting TNF-α, there is still a lot of room for progress. Need constant exploration and improvement.
Reference
- Pan Yuchen, Wang Jiali, Hou Yayi. A. (2017). The research and development of TNF-α in autoimmune disease. 41(12):883-889.
